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Protein key to harnessing regenerative power of blood stem cells identified by researchers
Nov 24, 2014
In a study led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member, Dr. John Chute, UCLA scientists have for the first time identified a unique protein that plays a key role in regulating blood stem cell replication in humans.
This discovery lays the groundwork for a better understanding of how this protein controls blood stem cell growth and regeneration, and could lead to the development of more effective therapies for a wide range of blood diseases and cancers.
The study was published online November 21, 2014 ahead of print in the Journal of Clinical Investigation.
Hematopoietic stem cells (HSCs) are the blood-forming cells that have the remarkable capacity to both self-renew and give rise to all of the differentiated cells (fully developed cells) of the blood system. HSC transplantation provides curative therapy for thousands of patients annually. However, little is known about the process through which transplanted HSCs replicate following their arrival in human bone marrow. In this study, the authors showed that a cell surface protein called protein tyrosine phosphatase-sigma (PTP-sigma) regulates the critical process called engraftment, meaning how HSCs start to grow and make health blood cells after transplantation.
http://www.sciencedaily.com/releases/2014/11/141124143414.htm
UT Southwestern cancer biologists link tumor suppressor gene to stem cells
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This news release is available on our home page at
utsouthwestern.edu/home/news/index.html
DALLAS – March 26, 2014 – Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.
The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.
In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery – tying the p53 gene to stem cells. Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53’s tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.
“The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function of p53 in stem cells,” said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern’s Graduate School of Biomedical Sciences. “We may, in fact, have some important answers for how p53 suppresses tumors.”
The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.
... p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. It regulates other genes, marshaling them to carry out an untold number of preemptive attacks and obliterate many pre-cancerous cells before they ever pose a threat. In nearly every case where there’s a tumor, p53 is damaged or deranged, strongly suggesting that it is a tumor suppressant.
Stem cells are one of the body’s most useful cells because of their regenerative capabilities. Stem cells produce daughter cells, one that is a stem cell and another that can become virtually any kind of cell that’s needed, such as a blood cell or a kidney cell. Stem cells have received tremendous attention in cancer research because of the stem cell hypothesis. That hypothesis maintains that malignant tumors are initiated and maintained by a population of tumor cells that have properties similar to adult stem cells.
“What this new finding tells us is that an ancient functionality of p53 was hard-wired into stem cell function,” said Dr. Abrams, senior author. “From the standpoint of trying to decipher cancer biology, that’s a pretty profound observation.”
To study the gene, researchers in Dr. Abrams lab, including Dr. Annika Wylie, postdoctoral research fellow and first author on the paper, developed a transgenic sensor that makes cells glow when they are active in drosophila, or fruit flies. Other UT Southwestern researchers involved included Dr. Michael Buszczak, Assistant Professor of Molecular Biology.
The work was supported by the Cancer Prevention and Research Institute of Texas, the Ellison Foundation, the National Institute of General Medical Sciences, the Welch Foundation, the National Institute of General Medical Sciences, and a Genetic Training Grant.
UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated cancer center in North Texas. The center brings innovative cancer care to the region, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
Discovery of Reprogramming Signature May Help Overcome Barriers to Stem Cell-Based Regenerative Medicine
http://www.sciencedaily.com/releases/2012/09/120918184749.htm
Salk scientists have identified a unique molecular signature in induced pluripotent stem cells (iPSCs), "reprogrammed" cells that show great promise in regenerative medicine thanks to their ability to generate a range of body tissues.
In this week's Proceedings of the National Academy of Sciences, the Salk scientists and their collaborators at University of California, San Diego, report that there is a consistent, signature difference between embryonic and induced pluripotent stem cells. The findings could help overcome hurdles to using the induced stem cells in regenerative medicine.
"We believe that iPSCs hold a great potential for the treatment of human patients," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and the senior author on the paper. "Yet we must thoroughly understand the molecular mechanisms governing their safety profile in order to be confident of their function in the human body. With the discovery of these small, yet apparent, epigenetic differences, we believe that we are now one step closer to that goal."
Embryonic stem cells (ESCs) are known for their "pluripotency," the ability to differentiate into nearly any cell in the body. Because of this ability, it has long been thought that ESCs would be ideal to customize for therapeutic uses. However, when ESCs mature into specific cell types, and are then transplanted into a patient, they may elicit immune responses, potentially causing the patient to reject the cells.
In 2006, scientists discovered how to revert mature cells, which had already differentiated into particular cell types, such as skin cells or hair cells, back into a pluripotent state. These "induced pluripotent stem cells" (iPSCs), which could be developed from the patient's own cells, would theoretically carry no risk of immune rejection.
However, scientists found that iPSCs had molecular differences from embryonic stem cells. Specifically, there were epigenetic changes, chemical modifications in DNA that might alter genetic activity. At certain points in the iPSC's genome, scientists could see the presence of different patterns of methyl groups when compared to the genomes of ESCs. It seemed these changes occurred randomly.
Izpisua Belmonte and his colleagues wanted to understand more about these differences. Were they truly random, or was there a discernable pattern?
Unlike previous studies, which had primarily analyzed iPSCs derived from only one mature type of cells (mainly connective tissue cells called fibroblasts), the Salk and UCSD researchers examined iPSCs derived from six different mature cell types to see if there were any commonalities. They discovered that while there were hundreds of unpredictable changes, there were some that remained consistent across the cell types: the same nine genes were associated with these common changes in all iPSCs.
"We knew there were differences between iPSCs and ESCs," says Sergio Ruiz, first author of the paper, "We now have an identifying mark for what they are."
The therapeutic significance of these nine genes awaits further research. The importance of the current study is that it gives stem cells researchers a new and more precise understanding of iPSCs.
Other researches on the study were: Dinh Diep (co-first author), Athurva Gore, Athanasia D. Panopoulos, Nuria Montserrat, Nongluk Plongthongkum, Sachin Kumar, Ho-Lim Fung, Alessandra Giorgetti, Josipa Bilic, Erika M. Batchelder, Holm Zaehres, Natalia G. Kan, Hans R. Schöler, Mark Mercola and Kun Zhang.
The work was supported by grants from the Instituto de Salud Carlos III, the Focht-Powell Fellowship, Fundacion Cellex, MINECO, Sanofi, the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, CIRM and NIH.
Looking in. B'marked.
Humanizing Stem Cell Politics
http://www.huffingtonpost.com/saleem-h-ali/stem-cell-research-politics-_b_1253540.html
As the election season heats up, the issue of stem cell research and the rights of embryos is once again taking traction. The Komen funding saga this past week suggests that we have yet another battle awaiting scientists and health professionals. Many political candidates are being held hostage by absolutist ideologies about the "right of embryonic cells" despite exhortations by an overwhelming majority of scientists regarding the salience of such research for science. This polarization really hits home for me as the parent of a child who could easily benefit from such research, and who has examined the history of scientific advancement, acutely aware of the peril of "false hope."
Eight years ago this February our older son Shahmir (now aged 13) was diagnosed with Type-1 diabetes. His symptoms of excessive thirst during the winter months had mentally prepared me for the worst news to come from the doctor. My wife and I were caught in a torrent of emotional turmoil as we were told how Shahmir's life was to be dependent on a delicate balance of one indispensable molecule -- insulin. The most daunting challenge for us in keeping Shahmir healthy was to ensure that he got enough insulin but not too much. If he got even a few more units of insulin than his body needed, he could sink into hypoglycemic shock and risk sudden death.
Our sentiments swayed from denial, to anger to guilt to grief and finally acceptance of our predicament. The doctors assured us that there was nothing we could have done to prevent this illness since the complex confluence of genetic and environmental factors that cause Type-1 diabetes are very different from those that lead to the far more common and diet-related Type-2 diabetes. Shahmir was not obese or consuming excessive sweets, or displaying any unhealthy behavior patterns, yet he would now have to lead a life of tremendous discipline and self-denial in order to survive. After the initial months of grief had abated, we reconfigured our lives and returned to a tenuous sense of normalcy.
As an academic, my coping strategy for this situation was to find out as much as I could about diabetes and most importantly about insulin, which has relevance to current debates between stem-cell proponents and opponents. The Nobel Prize-winning discovery of this molecule in 1922 by Canadian researchers Frederick Banting, Charles Best and John Macleod is ranked among the most important medical achievements of all times. Millions of lives have been saved by the persistence of these men and their colleagues in numerous countries who struggled against all odds to extract the molecule and not be dissuaded by convention, ideology or political territoriality.
They were willing to persevere, even though many researchers before them had given up. Their allegiance to scientific methods as well as their willingness to collaborate with industry made it possible to mass produce insulin within a year of its discovery. The pharmaceutical company, Eli Lilly started producing bovine insulin through collaboration with the research team and a global effort was undertaken to distribute the life-saving medication. Long before the era of email networks or international organizations such as the United Nations, professionals from various fields united to work on an effective standardization of insulin and make it available globally at an affordable cost. In the words of medical historian Christiane Sinding, the standardization and distribution of insulin was "a result of the impressive working of a trans-disciplinary and trans-national network."
It is through such efforts of uniting in our common humanity that diabetics worldwide can now live relatively functional lives and contribute to human achievement, exemplified by U.S. Supreme Court Justice Sonia Sotomayor or Oscar-winning Hollywood star Halle Berry. Five years ago, William Cross, became the first Type-1 diabetic to summit Mount Everest -- perhaps the ultimate test of human physical accomplishment. Such inspirational stories give us hope that Shahmir will also have a fulfilled life. His regimen of insulin injections has been transitioned to a digital device that infuses the precious molecule into his body when needed. We still have to check his blood sugar several times a day but he now considers these to be more metaphoric "pin pricks" of life.
Global efforts to fight diseases and reduce human suffering should not be put on the altar of "slippery slope" politics or absolutist ethics. Science and human resilience have triumphed so far against diseases like Type 1 diabetes -- as the story of how insulin was discovered and distributed shows us. The next step towards finding a cure for this disease will require us to make the same kind of bold decisions that consider the greater good of science and human development. Appropriate bioethical procedures for approval must always be followed for research but the criteria for evaluation should be driven by objective metrics rather than theologically entrenched emotionalism.
Let's hope that all political candidates will agree to defer on such matters to scientists and existing bioethics frameworks within the U.S. health care system rather than playing political games with the lives of those who need our protection the most.
StemCells, Inc. Awarded $20 Million From the California Institute for Regenerative Medicine for Alzheimer's Disease Program
Award to Fund IND-Enabling Activities for the Company's HuCNS-SC(R) Neural Stem Cells in Alzheimer's Disease
NEWARK, Calif., Sept. 6, 2012 (GLOBE NEWSWIRE)
StemCells, Inc. (STEM) today announced that the California Institute for Regenerative Medicine (CIRM) has approved an award to the Company for up to $20 million under CIRM's Disease Team Therapy Development Award program (RFA 10-05). The award is to fund preclinical development of StemCells' proprietary HuCNS-SC(R) product candidate (purified human neural stem cells) in Alzheimer's disease over a maximum four-year period, with the goal of filing an investigational new drug (IND) application for a clinical trial in that time. In July, CIRM approved a separate award to the Company under RFA 10-05 for up to $20 million to fund preclinical development of HuCNS-SC cells in cervical spinal cord injury.
"With the recent spate of late-stage clinical failures in Alzheimer's disease, it is clear that the field could benefit from alternative approaches to lessen the huge burden on families, caregivers and our healthcare system," commented Martin McGlynn, President and CEO of StemCells, Inc. "Our recently reported preclinical data, which showed that our neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease, shows our approach has promise. We greatly appreciate the support from CIRM, which should help us accelerate our efforts to test our HuCNS-SC cells in Alzheimer's disease."
StemCells will evaluate its HuCNS-SC cells as a potential treatment for Alzheimer's disease in collaboration with Frank LaFerla, Ph.D., a world-renowned researcher in the field. Dr. LaFerla is Director of the University of California, Irvine (UCI) Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Chancellor's Professor, Neurobiology and Behavior in the School of Biological Sciences at UCI.
Mr. McGlynn added, "CIRM's approval of two awards to StemCells illustrates the tremendous promise of our neural stem cell technology and the high degree of confidence in the world class team of scientists and clinicians who will be working to translate this technology into potential treatments and cures for these devastating diseases."
About CIRM
CIRM was established in November 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The statewide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was overwhelmingly approved by voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities, and other vital research opportunities. A list of grants and loans awarded to date may be seen here: http://www.cirm.ca.gov/for-researchers/researchfunding.
About StemCells, Inc.
StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC(R) cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. In a Phase I clinical trial in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children, the Company has shown preliminary evidence of progressive and durable donor-derived myelination in all four patients transplanted with HuCNS-SC cells. The Company is also conducting a Phase I/II clinical trial in chronic spinal cord injury in Switzerland and recently reported positive interim data for the first patient cohort. The Company has also initiated a Phase I/II clinical trial in dry age-related macular degeneration (AMD), and is pursuing preclinical studies in Alzheimer's disease. StemCells also markets stem cell research products, including media and reagents, under the SC Proven(R) brand. Further information about StemCells is available at http://www.stemcellsinc.com
Production of Functional Classical Brown Adipocytes from Human Pluripotent Stem Cells using Specific Hemopoietin Cocktail without Gene
Cell Metabolism, Volume 16, Issue 3, 394-406, 5 September 2012
Copyright 2012 Elsevier Inc. All rights reserved.
10.1016/j.cmet.2012.08.001
VEGF, SCF, Flt3-L, and IL6 play roles in brown adipocyte (BA) differentiation
Human pluripotent stem cell (hPSC)-derived BAs improve lipid, glucose metabolism
hPSC-derived BAs serve as stroma for myeloid progenitor cells
ß-adrenergic receptor signaling promotes recovery from myelosuppression
Summary
Brown adipose tissue is attracting much attention due to its antiobestic effects; however, its development and involvement in metabolic improvement remain elusive. Here we established a method for a high-efficiency (>90%) differentiation of human pluripotent stem cells (hPSCs) into functional classical brown adipocytes (BAs) using specific hemopoietin cocktail (HC) without exogenous gene transfer. BAs were not generated without HC, and lack of a component of HC induced white adipocyte (WA) marker expressions. hPSC-derived BA (hPSCdBA) showed respiratory and thermogenic activation by ß-adrenergic receptor (AdrRß) stimuli and augmented lipid and glucose tolerance, whereas human multipotent stromal cell-derived WA (hMSCdWA) improved lipid but inhibited glucose metabolism. Cotransplantation of hPSCdBA normalized hMSCdWA-induced glucose intolerance. Surprisingly, hPSCdBAs expressed various hemopoietin genes, serving as stroma for myeloid progenitors. Moreover, AdrRß stimuli enhanced recovery from chemotherapy-induced myelosuppression. Our study enhances our understanding of BA, identifying roles in metabolic and hemogenic regulation.
Authors
Miwako Nishio, Takeshi Yoneshiro, Masako Nakahara, Shinnosuke Suzuki, Koichi Saeki, Mamoru Hasegawa, Yuko Kawai, Hidenori Akutsu, Akihiro Umezawa, Kazuki Yasuda, Kazuyuki Tobe, Akira Yuo, Kazuo Kubota, Masayuki Saito, Kumiko SaekiSee AffiliationsHint: Rollover Authors and Affiliations Department of Disease Control, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Department of Radiology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Laboratory of Histology and Cytology, Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
DNAVEC Corporation, Ibaraki 300-2511, Japan
LSI Sapporo Clinic, Sapporo 065-0013, Japan
Department of Reproductive Biology, Center for Regenerative Medicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
The First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Sapporo 065-0013, Japan
Corresponding authorHighlights
Stem Cells Bring New Hope for Parry-Romberg Syndrome Patients
A study led by Dr. Ko and Dr. Choi of Asan Medical Center and Dr. Ra of RNL Stem Cell Technology Institute posted on the 'Annals of Plastic Surgery' ..posted by PoemStone on the Medical World News board here on IHUB....
http://finance.yahoo.com/news/stem-cells-bring-hope-parry-043700938.html
SEOUL, South Korea, Aug. 31, 2012 /PRNewswire/ In a landmark clinical study, scientists of the RNL Stem Cell Technology Institute have demonstrated that the transplant of patients' own ("autologous") stem cells can dramatically improve the ability of plastic surgeons to repair diseases. In the September 2012 issue of the prestigious international plastic surgery journal Annals of Plastic Surgery (69:3), researchers published their controlled study of the power of stem cells, describing a breakthrough with patients who have Parry-Romberg Syndrome. More than 200,000 have this tragic and debilitating disease in the U.S. alone. Their prognosis without treatment is the slow loss of control, then paralysis of the face and in some cases the mouth and even eyes. Most patients with Parry-Romberg begin to experience these symptoms between the age of five (5) and fifteen (15) years of age. There is, says the National Institute of Neurological Disorders and Stroke of the U.S. National Institutes of Health, "no cure." To date, treatments have involved waiting until the disease slows and then transplanting fat into patients' faces, strengthening bones in their faces, and using microvascular surgery to "install" a free flap of skin.
However the only solution for patients with this disorder, and those with similar disorders, the grafting of fat, is at best a temporary solution, which alleviates none of the pain felt by these patients, and can in fact result in an increase in pain when fat grafts fail. So, plastic surgeons, engineers and others have searched for years for a solution with longer term effects, or even a way to fight the disease's symptoms in a sustained way.
Dr. Kyeung-Suk Ko and Dr. Jong-Woo Choi led a research team under Dr. Jeong-chan Ra of RNL Stem Cell Technology Institute that may have uncovered, for the first time, just such a tool for plastic surgeons: patients' own stem cells. In their controlled study, the team painlessly removed a few ounces of fat from one group Parry-Romberg Syndrome patients, harvesting stem cells from these patients' fat, cells that are genetically identical to the patient's cells throughout their body and that have well documented abilities to "home in" on inflammation and disease and have dramatic effects on patients' symptoms and even disease itself. In this study, those patients in the "treated" group received stem cells magnified into the millions (using the team's patented technology whose safety has been well published). These patients' outcomes, adding stem cells to standard-of-care therapies, were measured against traditional microfat grafts in the control group receiving no stem cells.
In what many have described as a revolutionary finding, the team found that those patients who received their own "adult" mesenchymal stem cells saw unprecedented improvement in the effectiveness of therapies. Fat grafts that are often "resorbed" into patients' skin shortly after they are placed were 50% less likely to disappear when provided alongside stem cells (20.59% vs 46.81%).
This study was approved by the Korea Food and Drug Administration, the institutional IRB of the Asan Medical Center, and peer-reviewed prior to acceptance in the renowned plastic surgery publication under the title: "Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg Disease) with microfat grafting techniques using three-dimensional computed tomography and three-dimensional camera." Authors and investigators included: Koh KS, Oh TS, Kim H, Chung IW, Lee KW, Lee HB, Park EJ, Chung JS, Shin IS, Ra JC, Choi JW. Media and others may access the article at http://journals.lww.com/annalsplasticsurgery/Abstract/2012/09000/Clinical_Application_of_Human_Adipose.22.aspx. Its National Library of Medicine ID is PMID:22878516.
Dr. Ra, senior author, said, "We believe that this is a big step for Parry-Romberg Syndrome patients and expect to see autologous stem cell transplantation as standard of care for their treatment. The next step is to test the efficacy of the many ways in which stem cells from adults' own bodies will expand the quality of life and even identify cures for many rare diseases
StemCells, Inc. Announces Its Human Neural Stem Cells Restore Memory in Models of Alzheimer's Disease
NEWARK, Calif., July 17, 2012 (GLOBE NEWSWIRE) --
StemCells, Inc. (Nasdaq:STEM), today announced preclinical data demonstrating that its proprietary human neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease (AD). The data was presented today at the Alzheimer's Association International Conference 2012 in Vancouver, Canada.
The study results showed that transplanting the cells into a specific region of the brain, the hippocampus, statistically increased memory in two different animal models. The hippocampus is critically important to the control of memory and is severely impacted by the pathology of AD. Specifically, hippocampal synaptic density is reduced in AD and correlates with memory loss. The researchers observed increased synaptic density and improved memory post transplantation. Importantly, these results did not require reduction in beta amyloid or tau that accumulate in the brains of patients with AD and account for the pathological hallmarks of the disease.
The research was conducted in collaboration with a world-renowned leader in AD, Frank LaFerla, Ph.D., Director of the University of California, Irvine (UCI) Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Chancellor's Professor, Neurobiology and Behavior in the School of Biological Sciences at UCI. Matthew Blurton-Jones, Ph.D., Assistant Professor, Neurobiology and Behavior at UCI, presented the study results.
"This is the first time human neural stem cells have been shown to have a significant effect on memory," said Dr. LaFerla. "While AD is a diffuse disorder, the data suggest that transplanting these cells into the hippocampus might well benefit patients with Alzheimer's. We believe the outcomes in these two animal models provide strong rationale to study this approach in the clinic and we wish to thank the California Institute of Regenerative Medicine for the support it has given this promising research."
Stephen Huhn, M.D., FACS, FAAP, Vice President and Head of the CNS Program at StemCells, added, "While reducing beta amyloid and tau burden is a major focus in AD research, our data is intriguing because we obtained improved memory without a reduction in either of these pathologies. AD is a complex and challenging disorder. The field would benefit from the pursuit of a diverse range of treatment approaches and our neural stem cells now appear to offer a unique and viable contribution in the battle against this devastating disease."
About Alzheimer's Disease
Alzheimer's disease is a progressive, fatal neurodegenerative disorder that results in loss of memory and cognitive function. Today there is no cure or effective treatment option for patients afflicted by Alzheimer's disease. According to the Alzheimer's Association, approximately 5.4 million Americans have Alzheimer's disease, including nearly half of people aged 85 and older. The prevalence of Alzheimer's disease is expected to increase rapidly as a result of the country's aging population.
About StemCells, Inc.
StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC® cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. In a Phase I clinical trial in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children, the Company has shown preliminary evidence of progressive and durable donor-derived myelination in all four patients transplanted with HuCNS-SC cells. The Company is also conducting a Phase I/II clinical trial in chronic spinal cord injury in Switzerland and recently reported positive interim safety data for the first patient cohort. The Company has also initiated a Phase I/II clinical trial in dry age-related macular degeneration (AMD), and is pursuing preclinical studies in Alzheimer's disease. StemCells also markets stem cell research products, including media and reagents, under the SC Proven® brand. Further information about StemCells is available at http://www.stemcellsinc.com.
UT Southwestern researchers identify mechanism that
maintains stem cells readiness, helps leukemia cells growth
This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html
DALLAS – May 31, 2012 – An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.
“Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers,” said Dr. Chengcheng “Alec” Zhang, assistant professor in UT Southwestern’s departments of physiology and developmental biology. “Our research identified a protein receptor on cancer cells that induces differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers.”
The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.
“The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia,” he said.
Stemness refers to the blood stem cells’ potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.
Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as “orphans,” he said.
The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car’s brakes.
In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don’t use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells’ other major activity, Dr. Zhang said. He stressed that the inhibition doesn’t cause them to create new stem cells but does preserve their potential to do so.
In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors’ action only in leukemia.
Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cantó and Dr. E. Sally Ward, professor of immunology.
Former UT Southwestern researchers include lead author and former instructor of physiology Dr. Junke Zheng, now at Shanghai Jiao Tong University School of Medicine in Shanghai, China; Dr. Masato Umikawa, now at the University of Ryukyus in Okinawa, Japan; Dr. Shu-Hsia Chen, now at Mount Sinai School of Medicine in New York City; Dr. Huan-You Wang, now at the University of California, San Diego; and Dr. Jingxiao Ye, now at the University of Texas at Dallas.
The study received funding from the National Institutes of Health; the American Society of Hematology Junior Faculty Award; March of Dimes Basil O’Connor Scholar Award; the Department of Defense; the Cancer Prevention and Research Institute of Texas; and the Gabrielle’s Angel Foundation.
Visit www.utsouthwestern.org/cancer to learn more about UT Southwestern’s clinical services in cancer.
Aged Hematopoietic Stem Cells Rejuvenated to Be Functionally Younger
http://www.sciencedaily.com/releases/2012/05/120503125808.htm
Researchers have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day fend off some ailments of old age..
Scientists at Cincinnati Children's Hospital Medical Center and the Ulm University Medicine in Germany report their findings online May 3 in the journal Cell Stem Cell. The paper brings new perspective to what has been a life science controversy countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention.
HSCs are stem cells that originate in the bone marrow and generate all of the body's red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous but less effective at regenerating blood cells and immune cells. This makes older people more susceptible to infections and disease, including leukemia.
Researchers in the current study determined a protein that regulates cell signaling Cdc42 also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells, explained Hartmut Geiger, PhD, the study's principal investigator and a researcher in the Division of Experimental Hematology/Cancer Biology at Cincinnati Children's, and the Department of Dermatology and Allergic Diseases, Ulm University Medicine.
"Aging is interesting, in part because we still don't understand how we age," Geiger said. "Our findings suggest a novel and important role for Cdc42 and identify its activity as a target for ameliorating natural HSC aging. We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body."
The findings are early and involve laboratory manipulation of mouse cells, so it remains to be seen what direct application they may have for humans. Still, the study expands what is known about the basic molecular and cellular mechanisms of aging a necessary step to one day designing rational approaches to aiding a healthy aging process.
One reason the research team focused on Cdc42 is that previous studies have reported elevated activity of the protein in various tissue types of older mice which have a natural life span of around two years. Also, elevated expression of Cdc42 has been found in immune system white blood cells in older humans.
In the current study, researchers found elevated activity of Cdc42 in the HSCs of older mice. They also were able to induce premature aging of HSCs in mice by genetically increasing Cdc42 activity in the cells. The aged cells lost structural organization and polarity, resulting in improper placement and spacing of components inside the cells. This disorganization contributed to the cells' decreased functional efficiency.
The researchers then analyzed HSCs from older mice to see if inhibition of Cdc42 would reverse the aging process. They used a specific dose (5uM) of a pharmacologic inhibitor of Cdc42, CASIN, to reduce the protein's activity in the cells -- processing them for 16 hours ex vivo in laboratory cultures. This improved structural organization, increased polarity and restored functionality in the older cells to levels found in young cells.
To test the rejuvenated cells, the researchers used a process known as serial competitive transplantation. This included extracting HSCs from young (2-4 months) and aged (20-26 months) mice and processing them in laboratory cultures. Young and rejuvenated cells were then engrafted into recipient mice. This allowed scientists to compare how well young and rejuvenated aged HSCs started to repopulate and transform into different types of blood cells. It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells.
Researchers next plan to test the Cdc42 inhibitor, CASIN, in mice to see how HSCs and various tissues in the laboratory models respond. In particular, they are testing red blood cell production, endurance and immune response in the mice. The research team is also acquiring samples of human HSCs to see how those cells respond in laboratory tests to Cdc42 expression.
The first author on the study was Maria Carolina Florian, PhD, from the University of Ulm. Also collaborating were Karin Doerr, Anja Niebel, Deidre Daria, Hubert Schrezenmeier, MD, PhD, Markus Rojewski and Karin Sharffetter-Kochanek, all from the University of Ulm, and Yi Zheng, PhD, and Marie-Dominique Filippi, PhD, of Cincinnati Children's.
Funding support for the research came from the Deutsche Forschungsgemeinschaft and the National Institutes of Health.
Stem Cell Treatment Might Reverse Heart Attack Damage
By By Mary Brophy Marcus
http://news.yahoo.com/stem-cell-treatment-might-reverse-heart-attack-damage-000807218.html
(HealthDay News) .. Stem cell therapy's promise for healing damaged tissues may have gotten a bit closer to reality. In a small, early study, heart damage was reversed in heart-attack patients treated with their own cardiac stem cells, researchers report.
The cells, called cardiosphere-derived stem cells, regrew damaged heart muscle and reversed scarring one year later, the authors say.
Up until now, heart specialists' best tool to help minimize damage following a heart attack has been to surgically clear blocked arteries.
"In our treatment, we dissolved scar and replaced it with living heart muscle. Such 'therapeutic regeneration' has long been the holy grail of cell therapy, but had never been accomplished before; we now seem to have done it," said study author Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles.
However, outside experts cautioned that the findings are preliminary and the treatment is far from ready for widespread use among heart-attack survivors.
The study, published online Feb. 14 in The Lancet, involved 25 middle-aged patients (average age 53) who had suffered a heart attack. Seventeen underwent stem cell infusions while eight received standard post-heart attack care, including medication and exercise therapy.
The stem cells were obtained using a minimally invasive procedure, according to the researchers from Cedars-Sinai and the Johns Hopkins Hospital in Baltimore.
Patients received a local anesthetic and then a catheter was threaded through a neck vein down to the heart, where a tiny portion of muscle was taken. The sample provided all the researchers needed to generate a supply of new stem cells -- 12 million to 25 million -- that were then transplanted back into the heart-attack patient during a second minimally invasive procedure.
One year after the procedure, the infusion patients' cardiac scar sizes had shrunk by about half. Scar size was reduced from 24 percent to 12 percent of the heart, the team said. In contrast, the patients receiving standard care experienced no scar shrinkage.
Initial muscle damage and healed tissue were measured using MRI scans.
After six months, four patients in the stem-cell group experienced serious adverse events compared with only one patient in the control group. At one year, two more stem-cell patients had a serious complication. However, only one such event, a heart attack might have been related to the treatment, according to the study.
In a news release, Marban said that "the effects are substantial and surprisingly larger in humans than they were in animal tests."
Other experts were cautiously optimistic. Cardiac expert Dr. Bernard Gersh, a professor of medicine at Mayo Clinic, is not affiliated with the research but is familiar with the findings.
"This study demonstrates that it is safe and feasible to administer these cardiac-derived stem cells and the results are interesting and encouraging," he said.
Another specialist said that while provocative and promising, the findings remain early, phase-one research. "It's a proof-of-concept study," said interventional cardiologist Dr. Thomas Povsic, an assistant professor of medicine at the Duke Clinical Research Institute, in Durham, N.C.
And Dr. Chip Lavie, medical director of Cardiac Rehabilitation and Prevention at the John Ochsner Heart and Vascular Institute, in New Orleans, also discussed the results. He said that while the study showed that the cardiac stem cells reduced scar tissue and increased the area of live heart tissue in heart attack patients with moderately damaged overall heart tissue, it did not demonstrate a reduction in heart size or any improvement in the heart's pumping ability.
"It did not improve the ejection fraction, which is a very important measurement used to define the overall heart's pumping ability," Lavie noted. "Certainly, much larger studies of various types of heart attack patients will be needed before this even comes close to being a viable potential therapy for the large number of heart attack initial survivors."
Povsic concurred that much larger studies are needed. "The next step is showing it really helps patients in some kind of meaningful way, by either preventing death, healing them or making them feel better."
It's unclear what the cost will be, Povsic added. "What society is going to be willing to pay for this is going to be based on how much good it ends up doing. If they truly regenerate a heart and prevent a heart transplant, that would save a lot money."
Marban, who invented the stem cell treatment, said the while it would not replace bypass surgery or angioplasty, "it might be useful in treating 'irreversible' injury that may persist after those procedures."
As a rough estimate, he said that if larger, phase 2 trials were successful, the treatment might be available to the general public by about 2016.
More information
The U.S. National Heart, Lung, and Blood Institute describes current heart attack treatment.
StemCells, Inc. Receives FDA Authorization for Age-Related Macular Degeneration Clinical Trial
NEWARK, Calif., Feb. 2, 2012 (GLOBE NEWSWIRE) --
StemCells, Inc. (Nasdaq:STEM) today announced that the U.S. Food and Drug Administration (FDA) has authorized the initiation of a Phase I/II clinical trial of the Company's proprietary HuCNS-SC® product candidate (purified human neural stem cells) in dry age-related macular degeneration (AMD), the most common form of AMD. AMD is the leading cause of vision loss and blindness in people over 55 years of age, and approximately 30 million people worldwide are afflicted with the disease. There are no approved treatments for dry AMD.
"With the approval of this trial, we have accomplished something truly unique in the stem cell field, which is the extension of clinical testing of our proprietary human neural stem cell platform to all three elements of the central nervous system: the brain, spinal cord and eye," said Martin McGlynn, President and CEO of StemCells, Inc. "The preclinical data supporting our IND is particularly compelling and we look forward to getting this trial underway."
The Phase I/II trial will evaluate the safety and preliminary efficacy of HuCNS-SC cells as a treatment for dry AMD. The trial will be an open-label, dose-escalation study, and is expected to enroll a total of 16 patients. The HuCNS-SC cells will be administered by a single injection into the space beneath the retina. Patients' vision will be evaluated using conventional methods of ophthalmological assessment at predetermined intervals over a one-year period. Patients will then be followed for an additional four years in a separate observational study.
Preclinical data submitted as part of the Company's Investigative New Drug application demonstrated that HuCNS-SC cells protect host photoreceptors and preserve vision in a well-established animal model of retinal disease that is relevant to dry AMD. HuCNS-SC transplants significantly protect against the degeneration of photoreceptors, the key cells of the eye involved in vision.
Moreover, the number of cone photoreceptors, which are responsible for central vision, remain constant over an extended period, consistent with the sustained visual acuity and light sensitivity observed. In humans, degeneration of the cone photoreceptors account for the unique pattern of visual loss in dry AMD. A summary of the Company's preclinical data was published in the February issue of the international peer-reviewed European Journal of Neuroscience, and is available online at http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2011.07970.x/abstract.
"We have published the preclinical evidence demonstrating that our human neural stem cells might offer a safe, effective and simple approach to treating AMD and other retinal diseases," said Stephen Huhn, MD, FACS, FAAP, Vice President and Head of the CNS Program at StemCells, Inc. "Our approach is to provide durable protection of photoreceptors, thereby preserving vision, as opposed to approaches that aim to replace photoreceptors or the retinal pigmented epithelial cells. Furthermore, our preclinical data supports our hypothesis that we can achieve clinical benefit with a single transplant in AMD patients."
Environment That Nurtures Blood-Forming Stem Cells' Growth Identified
http://www.sciencedaily.com/releases/2012/01/120125131033.htm
Jan. 25, 2012 .. Scientists with the new Children's Research Institute at UT Southwestern Medical Center have identified the environment in which blood-forming stem cells survive and thrive within the body, an important step toward increasing the safety and effectiveness of bone-marrow transplantation.
Natural killer cell
Institute investigators led by Dr. Sean Morrison asked which cells are responsible for the microenvironment that nurtures haematopoietic stem cells, which produce billions of new blood cells every day. The answer: endothelial and perivascular cells, which line blood vessels.
"Although scientists have searched for decades to identify the stem cell home, this is the first study to reveal the cells that are functionally responsible for the maintenance of blood-forming stem cells in the body," said Dr. Morrison, director of the new institute and senior author of the study available Jan. 26 in Nature. "This discovery will lead to the identification of the mechanisms by which cells promote stem cell maintenance and expansion."
Scientists already have determined how to make large quantities of stem cells and how to change these cells into those of the nervous system, skin and other tissues. But they have been stymied by similar efforts to make blood-forming stem cells. A key obstacle has been the lack of understanding about the microenvironment, or niche, in which blood-forming stem cells reside in the body.
In the first breakthrough from the Children's Research Institute, Dr. Morrison's laboratory addressed this issue by systematically determining which cells are the sources of stem cell factor, a protein required for the maintenance of blood-forming stem cells. His team swapped out the mouse gene responsible for stem cell factor with a gene from jellyfish that encodes green fluorescent protein. The cells that glowed green were endothelial and perivascular cells, revealing them as the creators of the niche that nurtures healthy blood-forming stem cells.
Additional lab work showed that blood-forming stem cells become depleted if stem cell factor is eliminated from either endothelial or perivascular cells. Loss of stem cell factor from both of these sources caused stem cells to virtually disappear.
The research has implications for bone marrow and umbilical cord blood transplants, Dr. Morrison said. If scientists can identify the remaining signals by which perivascular cells promote the expansion of blood-forming stem cells, then they may be able to replicate these signals in the laboratory. Doing so will make it possible to expand blood-forming stem cells prior to transplantation into patients, thereby increasing the safety and effectiveness of this widely used clinical procedure.
Dr. Morrison's paper is the first to emerge from the Children's Research Institute at UT Southwestern, a pioneering venture that combines the medical center's research prowess with the world-class clinical expertise of Children's Medical Center Dallas. Under Dr. Morrison's leadership, the institute is focusing on research at the interface of stem cell biology, cancer, and metabolism that has the potential to reveal new strategies for treating disease.
The institute currently has more than 30 scientists and will eventually include 150 scientists in 15 laboratories led by UT Southwestern faculty members. Dr. Morrison's lab focuses on adult stem cell biology and cancers of the blood, nervous system and skin.
The Nature paper's first author is Dr. Lei Ding, postdoctoral research fellow at the Children's Research Institute and the Howard Hughes Medical Institute. Scientists from the University of Michigan and Cold Spring Harbor Laboratory also contributed to the study, which was supported by the HHMI and the National Heart, Lung and Blood Institute.
Avastin, Sutent Increase Breast Cancer Stem Cells, Study Suggests
http://www.sciencedaily.com/releases/2012/01/120125101335.htm
Jan. 25, 2012 ... Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don't lead to longer survival, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.
The drugs Avastin and Sutent have been looked at as potential breast cancer treatments. But while they do shrink tumors and slow the time till the cancer progresses, the effect does not last, and the cancer eventually regrows and spreads.
"This study provides an explanation for the clinical trial results demonstrating that in women with breast cancer antiangiogenic agents such as Avastin delay the time to tumor recurrence but do not affect patient survival. If our results apply to the clinic, it suggests that in order to be effective, these agents will need to be combined with cancer stem cell inhibitors, an approach now being explored in the laboratory," says study author Max S. Wicha, M.D., director of the U-M Comprehensive Cancer Center.
The researchers treated mice with breast cancer using Avastin (bevacizumab) and Sutent (sunitinib), both of which work by stopping the growth and formation of blood vessels, a process called angiogenesis. The researchers found that tumors treated with these drugs developed more cancer stem cells, the small number of cells within a tumor that fuel a cancer's growth and spread and that are often resistant to standard treatment. Both the number of cancer stem cells and the percentage of cancer stem cells that make up the tumor increased after being treated with each of these therapies.
The researchers found that the cancer stem cells increased because of a cellular response to low oxygen, a condition called hypoxia. And they were able to determine the specific pathways involved in hypoxia that activate the cancer stem cells.
Results of the study appear online in the Proceedings of the National Academy of Sciences Early Edition.
The U.S. Food and Drug Administration recently revoked approval of Avastin for treating breast cancer, although the drug is approved for use in other types of cancer. The reversal was in response to clinical trials showing that the drug's benefit was short-lived, with breast cancer patients quickly relapsing and the cancer becoming more invasive and spreading further throughout the body. Overall, the drug did not help patients live any longer.
The current study suggests the possibility of combining anti-angiogenesis drugs with a cancer stem cell inhibitor to enhance the benefit of this treatment. The researchers are testing this approach in mice and preliminary data looks promising.
Breast cancer statistics: 209,060 Americans will be diagnosed with breast cancer this year and 40,230 will die from the disease, according to the American Cancer Society.
Erasing Signs of Aging in Human Cells Now a Reality
http://www.sciencedaily.com/releases/2011/11/111103120605.htm
Scientists have recently succeeded in rejuvenating cells from elderly donors (aged over 100). These old cells were reprogrammed in vitro to induced pluripotent stem cells (iPSC) and to rejuvenated and human embryonic stem cells (hESC): cells of all types can again be differentiated after this genuine "rejuvenation" therapy. The results represent significant progress for research into iPSC cells and a further step forwards for regenerative medicine.
Inserm's AVENIR "Genomic plasticity and aging" team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011.
Human embryonic stem cells (hESC) are undifferentiated multiple-function cells. They can divide and form all types of differentiated adult cells in the body (neurons, cardiac cells, skin cells, liver cells, etc.). Since 2007, a handful of research teams across the world have been capable of reprogramming human adult cells into induced pluripotent cells (iPSC), which have similar characteristics and potential to human embryonic stem cells (hESC). This kind of reprogramming makes it possible to reform all human cell types without the ethical restrictions related to using embryonic stem cells.
Until now, research results demonstrated that senescence (the final stage of cellular aging) was an obstacle blocking the use of this technique for therapeutic applications in elderly patients. Today, Inserm researcher Jean-Marc Lemaitre and his team have overcome this obstacle. The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific "cocktail" of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of "young" cells, both from the perspective of their proliferative capacity and their cellular metabolisms.
A cocktail of six genetic factors
Researchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier.
Using this new "cocktail" of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.
In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the "rejuvenated" characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).
"Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity," explains Jean-Marc Lemaitre who directs the Inserm AVENIR team.
The results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. "Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier." He concluded. "This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients." adds the researcher.
Experts grow whole tooth units using mouse stem cells
http://news.yahoo.com/experts-grow-whole-tooth-units-using-mouse-stem-161543952.html
Reuters HONG KONG (Reuters) Scientists in Japan said on Wednesday they have created teeth complete with connective fibers and bones by using mouse stem cells and successfully transplanted them into mice, a step they hope will lead to progress in stem cell research.
The entire tooth units, which were inserted into lower jaws of mice, attached successfully with jaw bones and the rats were able to chew normally, the researchers wrote in a paper in PLoS One (Public Library of Science).
"The bioengineered teeth were fully functional ... there was no trouble (with) biting and eating food after transplantation," wrote Masamitsu Oshima, assistant professor at the Research Institute for Science and Technology, Tokyo University of Science.
The researchers hope this is a step to help the development of new human organs grown from a patient's own cells.
"At present, researchers worldwide do not have the method to culture three-dimensional organs in vitro (outside the body)," Professor Takashi Tsuji, who led the research, wrote in his reply to questions from Reuters.
"It is important to develop technologies for the culture of the bioengineered organ ... for the realization of future organ replacement regenerative therapy."
Stem cells are the body's master cells and source of all cells and tissues. They are undifferentiated and experts believe they can generate all the cell types of the organ from which they originate.
Because of their ability to generate different types of cells and multiply and self-renew, scientists hope to harness stem cells to treat a variety of diseases and disorders, including cancer, diabetes and injuries.
FROM STEM CELLS TO WHOLE TOOTH UNITS
Tsuji's team removed two types of stem cells from the molar teeth of mice and grew them in the laboratory. To control the length and shape of the teeth, the cells were placed in a mold, where they grew into entire tooth units.
The entire tooth units were then transplanted into the lower jaws of one-month-old mice. They fused with the tissues and jaw bones around them after about 40 days, Tsuji said. Nerve fibers too could be detected in the new teeth.
Tsuji stressed the importance of finding the right "seed cells" for reparative therapy. In this case, entire tooth units could be grown because the stem cells were taken from molar teeth of mice -- where they later grew into enamel, dental bones and other parts that comprised a regular tooth unit.
In 2010, U.S. researchers created an artificial lung that rats used to breathe for several hours.
Key Molecule for Stem Cell Pluripotency Discovered
Journal Reference:
Torben Redmer, Sebastian Diecke, Tamara Grigoryan, Angel Quiroga-Negreira, Walter Birchmeier, Daniel Besser. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO reports, 2011; DOI: 10.1038/embor.2011.88
Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered what enables embryonic stem cells to differentiate into diverse cell types and thus to be pluripotent.
This pluripotency depends on a specific molecule E-cadherin, hitherto primarily known for its role in mediating cell-cell adhesion as a kind of "intracellular glue." If E-cadherin is absent, the stem cells lose their pluripotency. The molecule also plays a crucial role in the reprogramming of somatic cells (body cells) into pluripotent stem cells.
Somatic cell nuclear transfer
Dr. Daniel Besser, Prof. Walter Birchmeier and Torben Redmer from the MDC, a member of the Helmholtz Association, used mouse embryonic fibroblasts (MEFs) in their stem cell experiments. In a first step they showed that the pluripotency of these stem cells is directly associated with the cell-adhesion molecule E-cadherin. If E-cadherin is absent, the stem cells lose their pluripotency. In a second step the researchers investigated what happens when somatic cells that normally neither have E-cadherin nor are pluripotent are reprogrammed into a pluripotent stem cell state. In this reprogramming technique, somatic cells are converted into induced pluripotent stem cells (iPSCs). This new technique may help researchers avoid the controversies that come with the use of human embryos to produce human embryonic stem cells for research purposes.
The MDC researchers found that in contrast to the original cells, the new pluripotent cells derived from mouse connective tissue contained E-cadherin. "Thus, we have double proof that E-cadherin is directly associated with stem-cell pluripotency. E-Cadherin is necessary for maintaining pluripotent stem cells and also for inducing the pluripotent state in the reprogramming of somatic cells," Dr. Besser said. "If E-cadherin is absent, somatic cells cannot be reprogrammed into viable pluripotent cells." In addition, E-Cadherin can replace OCT 4, one of the signaling molecules until now considered indispensable for reprogramming.
Next, the MDC researchers want to find out to what extent E-cadherin also regulates human embryonic stem cells. "Understanding the molecular relationships is essential for using human somatic cells to develop stem cell therapy for diseases such as heart attack, Alzheimer's or Parkinson's disease or diabetes," Dr. Besser said.
Cell Host & Microbe, Volume 9, Issue 3, 223-234, 17 March 2011
Copyright © 2011 Elsevier Inc. All rights reserved.
10.1016/j.chom.2011.02.005
Referred to by: Profaning the Ultimate Sanctuary: HIV La...
Summary
HIV infection is characterized by gradual immune system collapse and hematopoietic dysfunction. We recently showed that HIV enters multipotent hematopoietic progenitor cells and establishes both active cytotoxic and latent infections that can be reactivated by myeloid differentiation. However, whether these multipotent progenitors include long-lived hematopoietic stem cells (HSCs) that could establish viral reservoirs for the life of the infected person remains unknown. Here we provide direct evidence that HIV targets long-lived HSCs and show that infected HSCs yield stable, multilineage engraftment in a xenograft model. Furthermore, we establish that the capacity to use the chemokine receptor CXCR4 for entry determines whether a virus will enter multipotent versus differentiated progenitor cells. Because HSCs live for the life span of the infected person and are crucial for hematopoietic health, these data may explain the poor prognosis associated with CXCR4-tropic HIV infection and suggest HSCs as long-lived cellular reservoirs of latent HIV.
Authors
Christoph C. Carter, Lucy A. McNamara, Adewunmi Onafuwa-Nuga, Mark Shackleton, James Riddell, Dale Bixby, Michael R. Savona, Sean J. Morrison, Kathleen L. CollinsSee AffiliationsHint: Rollover Authors and Affiliations Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA
Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, USA
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA
Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109, USA
Corresponding author
These authors contributed equally to this work
Present address: Division of Hematology/Oncology and Bone Marrow Transplantation, San Antonio Military Medical Center; Department of Internal Medicine, University of Texas Health Science Center, San Antonio, TX 78236, USAHighlights
CXCR4-tropic HIV infects multipotent hematopoietic stem/progenitor cells (HSPCs)
CCR5-tropic HIV has minimal capacity to infect multipotent HSPCs
CXCR4-tropic HIV-infected human HSCs stably engraft in SCID mice
Chronic viremia is associated with a decline in bone marrow cell counts in vivo
...................................................................
Stem cell researchers awarded $500K prize in NY
http://news.yahoo.com/s/ap/20110316/ap_on_sc/us_med_medical_prize
ALBANY, N.Y. – Three stem cell researchers have been awarded the annual Albany Medical Center Prize in Medicine and Biomedical Research for their pioneering work in human stem cells.
The winners announced Wednesday are Elaine Fuchs of Rockefeller University in New York City; James A. Thomson of the University of Wisconsin-Madison School of Medicine and Public Health; and Shinya Yamanaka of Kyoto University in Japan and Gladstone Institute of Cardiovascular Disease in San Francisco.
They will share $500,000, the largest award in medicine and science in the United States. The prize was established in 2000 by the late Morris "Marty" Silverman.
James Barba, president and CEO of the medical center, said their discoveries move medical researchers closer to new treatments for diseases such as diabetes, Parkinson's, spinal cord injury and cancer.
"The solutions to these debilitating diseases and many, many others that plague humans might very well be found through the science of stem cells," Barba said in a statement.
Stem cells are prized for their versatility. They can turn into any cell in the body.
Yamanaka and Thomson are credited with discovering in their separate labs how to genetically reprogram adult human cells back to an embryonic state. This discovery was reported as a major scientific breakthrough in 2007. The cell lines, now used in laboratories worldwide, promise to speed up stem cell research by offering an alternative to actual embryonic stem cells.
Fuchs' work has focused on the biology of stem cells. Her discoveries in understanding how stem cells make skin and hair and how they repair wounds have led her laboratory to the genetic bases of human skin disorders, including cancers.
ProtoKinetix AAGP Dramatically Increase Recovery Rate of Cryopreserved and Refrigerated Stem Cells <PKTX.OB>
newsml:reuters.com
VANCOUVER, British Columbia--(Business Wire)--
ProtoKinetix (OTCBB: PKTX) (www.protokinetix.com), a biotechnology company that
has developed and patented a family of synthetic anti-aging glycopeptides (AAGP)
for medicine and the biotechnology and cosmetic industries today announced, as a
follow up to recent news on the research done by ProtoKinetix` lead scientific
investigator, Dr. Samer Hussein, the Company announces some of his findings as
related to stem cell recovery.
Using a standard cryogenic protocol for stem cell storage, the addition of
2mg/ml of AAGP resulted in an extraordinary recovery of 87-percent. Traditional
recovery rates after cryopreservation with DMSO are typically between 30 and
40-percent.
In addition to the value of AAGP in cryopreservation (frozen to -196?C), a set
of trials designed to determine whether AAGP treated stem cells could survive
after refrigeration (4?C) were conducted. After 3-days of refrigeration,
untreated cells have a very high mortality rate. These trials found that AAGP
can significantly reduce cell death rate. AAGP demonstrated an impressive and
repetitive 8 to 12-times increase in cell viability and survivability.
"Preservation of stem cells is getting to be more and more popular given the
disease fighting regenerative ability of the stem cells. These results with AAGP
opens up an ever expanding market for ProtoKinetix which we fully intend to take
advantage of, said Ross L. Senior, President and CEO of ProtoKinetix, Inc.
About ProtoKinetix
ProtoKinetix, Inc. is a biotechnology company that has developed and patented a
family of synthetic anti-aging glycopeptides (AAGP) for medicine and the
biotechnology and cosmetic industries. PKTX`s primary focus is on the
therapeutic potential for AAGP in the treatment of Diabetes, inflammatory
diseases, skin protection and anti-aging.
I guess a year later, with nothing changed in regard to this, is "moving pretty quickly" in their eyes? LoL :)
Protein Essential for Cell Division in Blood-Forming Stem Cells Discovered
University of Michigan researchers have discovered that a protein known to regulate cellular metabolism is also necessary for normal cell division in blood-forming stem cells. Loss of the protein results in an abnormal number of chromosomes and a high rate of cell death.
The finding demonstrates that stem cells are metabolically different from other blood-forming cells, which can divide without the protein, Lkb1. This metabolic difference could someday be used to better control the behavior of blood-forming stem cells used in disease treatments, said Sean Morrison, director of the U-M Center for Stem Cell Biology, which is based at the Life Sciences Institute.
"This raises the possibility that, in the future, we may be able to modulate stem cell function, when treating degenerative diseases or when performing cell therapies, by altering the metabolism of the cells," said Morrison, a Howard Hughes Medical Institute investigator. "It opens up a whole new area of inquiry that, until now, had not been recognized."
Lkb1 is a protein kinase that acts as a tumor suppressor and coordinates cellular metabolism with cell growth. Specifically, Lkb1 (and another kinase called AMPK) helps maintain a balance between a cell's internal energy production and the process of cell division, sending signals to halt division when a cell lacks the energy needed to execute the process.
Few studies have examined stem cell metabolism. There's been a widespread assumption among biologists that basic metabolic processes are broadly similar in most cell types.
In many types of cells, deleting the genes that make Lkb1 and AMPK leads to tissue overgrowth and the formation of tumors, presumably because the cells no long receive signals telling them to stop dividing.
Morrison's team deleted the two genes in blood-forming stem cells of mice -- the first time these genes have been "knocked out" in stem cells -- then observed and measured the effects. Their results are reported in the Dec. 2 edition of the journal Nature.
"One obvious prediction you'd make, based on the outcome of previous studies, is that the cells would start to hyper-proliferate," said Daisuke Nakada, a research fellow at the U-M Life Sciences Institute and first author of the Nature paper.
"But that's not what we saw at all," Morrison said. "Deletion of the Lkb1 gene induced cell death in blood-forming stem cells, and the cells disappeared faster than anything we've ever seen before."
The observed cell death is likely due to defects in energy production within the stem cells, as well as another effect observed by Morrison's team. They found that knocking out the Lkb1 gene derailed the cell division process, leading to unhealthy daughter cells with the wrong number of chromosomes.
Normal cell division, known as mitosis, results in the separation of replicated chromosomes and the formation of two daughter nuclei with identical sets of chromosomes and genes. Inside the dividing cell's nucleus, a structure called a mitotic spindle pulls chromosomes into the daughter cells in an orderly fashion.
Morrison's team found that deleting Lkb1 resulted in mitotic chaos. Multiple mitotic spindles formed, pulling the chromosomes into a tangled mess.
"The cells that survive this mayhem have an abnormal number of chromosomes, which we think leads to the death of a lot of cells," Morrison said. "So Lkb1 is acutely required for blood-forming stem cells to divide properly."
In addition to Nakada and Morrison, the other author of the Nature paper is Thomas Saunders, a research assistant professor in the Department of Internal Medicine at the Medical School and managing director of U-M's Transgenic Animal Model Core.
The work was supported by the Howard Hughes Medical Institute. Flow cytometry was partially supported by a National Institutes of Health grant to the U-M Comprehensive Cancer Center. Nakada was supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science.
Two other papers examining Lkb1's role in regulating cellular metabolism in blood-forming stem cells appear in the same edition of Nature. Both papers are by Harvard University researchers and report results consistent with the U-M findings.
Stem Cell Institute (Cellmedicine) Successfully Treats Spinal Cord Injury Patient With Adult Stem Cells
Peer-Reviewed Joint Publication Between Stem Cell Clinic and American Researchers
PANAMA CITY(Marketwire - 11/25/10)
The Stem Cell Institute (www.cellmedicine.com) reported today recovery of a spinal cord injury patient that was treated with a unique combination stem cell treatment. The patient suffered a crush fracture of the L1 vertebral body on May 13th, 2008 after a single propeller engine airplane crash. As a result of the spinal cord injury, the patient had severe neuropathic pain, loss of sexual and bladder function, as well as loss of movement and sensation in the legs.
He was treated on Oct 31-Nov 20, 2008, Jan 21-30, 2009, and July 1-10, 2009 with an adult stem cell protocol. The patient underwent a progressive recovery of sensation, mobility, and sexual and bladder function subsequent to each cycle of stem cell administration. Currently the patient is capable of walking and neuropathic pain diminished substantially.
"The doctors at the Stem Cell Institute have changed my life.
After the accident there was no hope. Now I have a new lease on life," said Juan Carlos Murillo Rodriguez, the patient who was treated. "I have recently passed my physical and am flying again as a commercial pilot."
Details of the scientific rationale for the treatment, as well as protocols and outcomes may be found in the peer-reviewed paper "Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report" which was published in the International Archives of Medicine and is available online at http://www.intarchmed.com/content/pdf/1755-7682-3-30.pdf.
"It is my honor that such a team of internationally recognized opinion leaders in the area of stem cells such as Doctors Amit Patel, Michael Murphy and Thomas Ichim have co-authored this publication," said Dr. Jorge Paz Rodriguez, Medical Director of the Stem Cell Institute and co-author of the publication. "By combining our clinical experience with cutting-edge advances in molecular and cellular biology, we believe we have put forth a very innovative protocol that we anticipate will be attempted by other groups."
About Stem Cell Institute
Stem Cell Institute is one of the leading adult stem cell research and treatment centers in the world. Using our pioneering treatment methods and utilizing partnerships with universities and physicians across the world, Stem Cell Institute has already treated over 800 patients with stem cell therapy and the company continues to expand. Stem Cell Institute is located in Panama City, Panama.
Contact:
Contact InfoDr. Jorge Paz Rodriguez800 980 STEM (7836) Email Contactwww.cellmedicine.com
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Resurrection of a Stem-Cell Funding Barrier — Dickey–Wicker in Court
http://healthpolicyandreform.nejm.org/?p=12660&query=TOC
NEJM | September 15, 2010 | Topics: Health Law
George J. Annas, J.D., M.P.H.
Embryo research was born political. Expressions of shock and surprise at the August 23 ruling of federal district court judge Royce Lamberth enjoining federal funding of stem-cell research — which was based largely on his reading of an amendment to an appropriations bill — are thus not terribly persuasive.1 The amendment, known as the Dickey–Wicker amendment, provides that no federal funds can be expended by the National Institutes of Health (NIH) for “(1) the creation of a human embryo or embryos for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risks of injury or death.” The case is now, for the second time, before the Court of Appeals for the D.C. Circuit, which has temporarily lifted Lamberth’s injunction and is deciding whether to reinstate it while the courts determine the amendment’s legal meaning.
The creation and destruction of human embryos for research are deeply tied not only to political and religious debates concerning abortion, but also to in vitro fertilization (IVF). In 1979, during the Carter administration, the Ethics Advisory Board of the Department of Health, Education, and Welfare (forerunner of the Department of Health and Human Services) recommended that the government support research on embryos in order to study and improve IVF. Federal research funding was never authorized, and IVF was introduced to clinical medicine without a research phase. The Reagan administration dissolved the ethics board and ignored its recommendations. The issue was next taken up during the Clinton administration by an NIH Human Embryo Research Panel, which voted on 27 goals of embryo research and recommended 7 as “acceptable for federal funding” — but failed to produce a credible ethical justification for its recommendations, which were widely ignored.
Congress, however, responded to the report, and in 1996 President Bill Clinton signed the first appropriations bill containing the Dickey–Wicker amendment, named for its sponsors, Representatives Jay Dickey (R-AR) and Roger Wicker (R-MS). It has been added to NIH appropriations bills every subsequent year, just as the Hyde Amendment restricting abortion funding is added.
The derivation of stem cells from embryos involves destroying the embryo. In 2001, President George W. Bush authorized federal funding for human embryonic stem-cell (ESC) research but limited it to cell lines that had been derived before his August 9 speech — and specifically to cell lines from surplus IVF embryos used with the consent of the couple whose egg and sperm were used to create them. No one challenged this policy as a violation of Dickey–Wicker, perhaps because, as Bush said, the “life and death decision” for these embryos had already been made.
President Barack Obama was well aware that federal funding of ESC research represents a political flashpoint, but he had promised to rescind the Bush policy, and there is wide support for expanded federal funding of ESC research. When Obama announced his new policy authorizing funding for cell lines derived after August 2001 (if derived from surplus IVF embryos, without the use of federal funds), he knew he could be reawakening the funding debate. He expressed his hope that “Congress will act on a bipartisan basis to provide further support for this research.”
Congress has not acted. Instead, the debate has shifted to the courts, where the core question is whether the new Obama guidelines are consistent with Dickey–Wicker. Although he has not decided this question, Lamberth has said he believes Dickey–Wicker is “unambiguous” and does not permit the NIH “to separate the derivation of ESCs from research on the ESCs,” because “derivation of ESCs from an embryo is an integral step in conducting ESC research.” Whether he will change his mind after briefing, argument, and perhaps testimony — or whether the Court of Appeals will rule otherwise — remains to be seen. The Obama administration’s new guidelines are based on the political compromise of deriving ESCs only from surplus IVF embryos, and as part of this compromise, the NIH seems to have conceded that derivation is an integral part of stem-cell research, which is why it sets strict limits on the source of the embryos used and the quality of consent obtained. The political argument for permitting the use of surplus IVF embryos is that these embryos were created for a legitimate reproductive purpose, and when they’re no longer wanted for that purpose, their donation for research is ethically preferable to their destruction without any potential societal benefit.2 Of course, anyone who objects to the creation of embryos for IVF would also object to this compromise. Does Dickey–Wicker permit this political compromise as a matter of law?
President Clinton’s National Bioethics Advisory Commission argued in 1999 that it was not ethically reasonable to separate the derivation of stem cells for research from their use in research. The commission believed that the federal government should fund both, for at least as long as the embryos used were those “remaining after infertility treatments.” Their reasons were “the close connection in practical and ethical terms between derivation and use of the cells” and the hope that permitting funding for cell derivation could advance science in this area.3 Lawyers asked by the commission to examine the meaning of Dickey–Wicker concluded that the NIH’s distinction between derivation and use of human ESCs was a “reasonable” interpretation of the amendment — but that “there is no indication that either proponents or opponents [of ESC research] contemplated the situation . . . in which research that destroyed the embryo was separately conducted from research using the cells derived from the embryo.”
The Clinton panel’s report got less attention than it deserved because at that time the national debate was focused on creating research embryos through cloning (somatic-cell nuclear transfer). Bush’s Council on Bioethics concentrated on cloning, but it was also the only national ethics panel ever to discuss federal funding as an ethical (rather than political) issue. It concluded that “the decision to fund an activity is . . . a declaration of official national support and endorsement, a positive assertion that the activity in question is deemed by the nation as a whole . . . to be good and worthy.” Such rhetoric seems disconnected from special-interest legislation5; a more honest statement regarding federal funding is that since Roe v. Wade, funding for anything remotely related to abortion (and since no one is pregnant, embryo research is only remotely related) has become a potent political liability in Congress. Obama’s own ethics panel has sensibly stayed out of this political funding debate.
Three paths are open to proponents of federal funding for human ESC research. The first is to mount a vigorous defense in the ongoing lawsuit, aiming to persuade the courts that the Obama administration’s interpretation of Dickey–Wicker is correct. But since victory is uncertain, the Obama administration should simultaneously aggressively seek congressional authorization for its current regulations. The vehicle could be a bill proposed by Representative Diana DeGette (D-CO), which authorizes research on stem cells derived from surplus IVF embryos; it has been passed twice (and vetoed by Bush) and would certainly be signed by Obama. Because this approach would retain Dickey–Wicker, however, and could thus lead to more legal challenges, it would be preferable (and probably more politically feasible) to amend Dickey–Wicker by adding language such as the following: “Nothing in part (2) prohibits the NIH from funding research using embryos created for procreation, including the derivation of stem cells, when the couple no longer wants to use them for procreation and has provided their informed authorization for them to be used in NIH-funded research.” Doing so would legislatively adopt the ethics position of the Clinton bioethics commission. The third path is continued reliance on private and state funding until sufficient scientific progress is made that the public demands federal funding for this research.
NIH Director Francis Collins has said that this issue “goes beyond politics . . . to patients and their families who are counting on us to do everything in our power, ethically and responsibly, to learn how to transform these cells into entirely new therapies.” This argument, of course, is itself political, and if Collins is right, the only place to resolve the funding issue is in Congress.
This article (10.1056/NEJMp1010466) was published on September 15, 2010, at NEJM.org.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
Source Information
From the Department of Health Law, Bioethics, and Human Rights, Boston University School of Public Health, Boston.
References
Sherley v. Sebelius, 2010 U.S. Dist. LEXIS 86441 (Aug. 23, 2010).
Annas GJ, Caplan A, Elias S. The politics of human-embryo research — avoiding ethical gridlock. N Engl J Med 1996;334:1329-1332
Full Text | Web of Science | Medline
Ethical issues in human stem cell research. Vol. 1. Report and recommendations of the National Bioethics Advisory Commission. Rockville, MD: National Bioethics Advisory Commission, 1999.
Flannery EJ, Javitt GH. Analysis of federal laws pertaining to funding of human pluripotent stem cell research. In: National Bioethics Advisory Commission. Ethical issues in human stem cell research Vol. 2. Commissioned papers. Rockville, MD: National Bioethics Advisory Commission, 2000:D-1–D-13.
Annas GJ, Elias S. Politics, moral and embryos: can bioethics in the United State rise above politics? Nature 2004;431:19-20
CrossRef | Web of Science | Medline
Judge refuses to lift ban on government stem cell funds
http://news.yahoo.com/s/nm/20100908/hl_nm/us_usa_stemcells_injunction
WASHINGTON (Reuters) – A U.S. judge refused on Tuesday to lift a ban on federal funding of human embryonic stem cell research despite Obama administration warnings it would set back key research and cost more than a thousand jobs.
U.S. District Judge Royce Lamberth rejected the Obama administration's emergency request to lift his injunction while the government appeals his ruling that barred federal funding.
The administration was "incorrect about much of their 'parade of horribles' that will supposedly result from this court's preliminary injunction," Lamberth said in a brief order.
The Obama administration had told Lamberth scores of research projects involving hundreds of millions of dollars in federal funding were affected by his injunction and more than 1,300 jobs were at risk.
A Justice Department spokesman had no immediate comment. The Obama administration could file an appeal with the U.S. Court of Appeals for the District of Columbia Circuit and ask that it lift the injunction.
President Barack Obama opened the door to broader federal funding of human embryonic stem cell research as one of his first acts after taking office in 2009, overturning his predecessor George W. Bush's limitations on the work.
The National Institutes of Health issued guidelines for the research, which Dr. James Sherley, a biological engineer at Boston Biomedical Research Institute, and Theresa Deisher, of Washington-based AVM Biotechnology, then challenged.
The two, who oppose human embryonic stem cell research, argued the expansion by NIH unfairly hurt their ability to win federal funding for their own work and violated legal restrictions barring research that involved destroying human embryos.
Lamberth agreed and issued his injunction last month. He defended it in his order Tuesday saying that granting a stay "would flout the will of Congress" and that while lawmakers could change the statute, "this court is not free to do so."
The judge also noted that Sherley and Deisher acknowledged in court filings that projects that have previously received funding were not affected by his injunction.
Supporters of human embryonic stem cell research say it is vital to carry it out alongside other types of stem cell research to understand how to transform cells into desired tissue types and treat diseases ranging from juvenile diabetes to blindness.
Opponents say it is wrong to destroy human embryos, even days-old embryos to be discarded from fertility clinics.
The Covenant...Francis Collins, a fervent Christian, thought he had resolved the stem-cell debate. A federal judge disagreed.
http://www.newyorker.com/reporting/2010/09/06/100906fa_fact_boyer#ixzz0yrFmPfjU
by Peter J. Boyer
September 6, 2010 Text Size:
The choice of Collins to head the N.I.H. seemed to reflect the President’s own view of the harmony between science and religion.
When the geneticist Francis Collins was named director of the National Institutes of Health, last summer, he became the public face of American science and the keeper of the world’s deepest biomedical-research-funding purse. He was praised by President Obama and waved through the Senate confirmation process without objection. There also came a peer review of a sort that he’d never experienced, conducted in the press and in Internet science forums. Collins read in the Times that many of his colleagues in the scientific community believed that he suffered from “dementia.” Steven Pinker, a cognitive psychologist at Harvard, questioned the appointment on the ground that Collins was “an advocate of profoundly anti-scientific beliefs.” P. Z. Myers, a biologist at the University of Minnesota at Morris, complained, “I don’t want American science to be represented by a clown.”
Collins’s detractors did not question his professional achievements, which long ago secured his place in the first rank of international scientists. As a young researcher at Yale, Collins conceived a method of hastening the laborious process of hunting disease-causing genes by skipping across long stretches of chromosomes until the suspect gene’s neighborhood was located. As an assistant professor at the University of Michigan, in the nineteen-eighties, he and collaborators at the University of Toronto employed this method to find the gene that causes cystic fibrosis and, a year later, the genetic flaw responsible for neurofibromatosis. These breakthroughs brought him fame and, eventually, the job of director of the Human Genome Project, which promised to revolutionize medicine by identifying and mapping all the approximately twenty thousand human genes that code for protein.
Thanks to that job, there wasn’t much doubt about Collins’s ability to handle the formidable management challenge of running the N.I.H., which directly employs twenty thousand scientists and staff, funds three hundred and twenty-five thousand outside researchers, and operates twenty-seven institutes and research centers on its campus, in Bethesda, Maryland. A key duty of the N.I.H. director is to justify the agency’s budget and defend before Congress the programs it funds, a duty that requires a skill quite apart from prowess in the laboratory. In fifteen years at the National Human Genome Research Institute, Collins had proved himself an able manager, bringing the Genome Project to a successful conclusion in 2003—two and a half years early and four hundred million dollars under budget. He also won friends in Congress with a genial manner and a gift for conveying complex scientific information in felicitous language.
The objection to Collins was his faith—or, at least, the ardency of it. Collins is a believing Christian, which places him in the minority among his peers in the National Academy of Science. (Of its members, according to a study, only seven per cent believe in God.)
After leaving the Genome Research Institute, Collins began drawing large crowds on the college lecture circuit; he created a Web site, BioLogos, to advance his idea of the companionability of reason and faith; and he wrote a best-selling book, “The Language of God,” in which he presented what he claims to be scientific evidence of the existence of God.
President Obama’s choice of Collins for the N.I.H. touched a nerve.
The George W. Bush era had been an extraordinarily fractious time in public science, beginning with Bush’s first prime-time address to the nation, in which he announced restrictions on embryonic-stem-cell research. That move, and others that followed, convinced Bush’s critics that the religious right had become the final arbiter of public policy, an impression that Bush seemed little inclined to dispel. “Well, we thought we’d seen the last of the theocracy of George W. Bush, but it apparently ain’t so,” Dr. Jerry Coyne, a University of Chicago professor, wrote when Collins was appointed. “I am funded by the N.I.H., and I’m worried. Not about my own funding (although I’m a heathen cultural Jew), but about how this will affect things like stem-cell research and its funding.”
A year later, Obama’s appointment of Collins seemed an inspired choice. The President had found not only a man who reflected his own view of the harmony between science and faith but an evangelical Christian who hoped that the government’s expansion of embryonic-stem-cell research might bring the culture war over science to a quiet end. On August 23rd, however, Judge Royce C. Lamberth, of the Federal District Court for the District of Columbia, halted federal spending for embryonic-stem-cell research, putting hundreds of research projects in limbo and plunging the N.I.H. back into a newly contentious national debate.
At the N.I.H., the ability to deal with controversies, as a generation of Collins’s predecessors learned, matters at least as much as credentials; political combat comes with the job. Collins does not seem a likely combatant. His physical aspect—gray mustache and hair (cut in an early-Beatles mop top), thin-rimmed eyeglasses, and a distinct pallor—suggests a man best acquainted with a sunless existence in some laboratory. Yet, in a relatively colorless town, Collins has come to be known as something of a character, a model of geek cool. He likes big, noisy motorcycles, and, despite a mild manner, he is famously unself-conscious. At the unlikeliest moments, he will strap on a guitar and accompany himself in song, often a tune he has composed for the occasion.
In dealing with Congress, Collins is less given to sentiment. A few weeks after moving into the director’s office, he received a letter from two Republican congressmen pressing him about a handful of N.I.H. grants “that do not seem to be of the highest scientific rigor.” The lawmakers, Joe Barton, of Texas, and Greg Walden, of Oregon, demanded to know the process by which the agency had funded a $423,500 study of why young heterosexual men did not consistently use condoms during sex. Barton and Walden were also curious about an N.I.H.-funded study investigating substance use and H.I.V.-risk behaviors among female and transgender sex workers in Thailand, and a $29,469 grant to researchers studying patterns of drug abuse in the Brazilian rave culture. The Barton-Walden inquiry was, in practical terms, just a gesture, as the programs in question had already been funded. Sometimes, though, such a gesture hits a vein of real political opportunity.
Gene Regulating Human Brain Development Identified
http://www.sciencedaily.com/releases/2010/07/100701131159.htm
ScienceDaily (July 4, 2010) — With more than 100 billion neurons and billions of other specialized cells, the human brain is a marvel of nature. It is the organ that makes people unique.
Now, writing in the journal Cell Stem Cell (July 1, 2010), a team of scientists from the University of Wisconsin-Madison has identified a single gene that seems to be a master regulator of human brain development, guiding undifferentiated stem cells down tightly defined pathways to becoming all of the many types of cells that make up the brain.
The new finding is important because it reveals the main genetic factor responsible for instructing cells at the earliest stages of embryonic development to become the cells of the brain and spinal cord. Identifying the gene -- known as Pax6 -- is a first critical step toward routinely forging customized brain cells in the lab.
What's more, the work contrasts with findings from animal models such as the mouse and zebrafish, pillars of developmental biology, and thus helps cement the importance of the models being developed from human embryonic stem cells.
The new work, conducted in the Waisman Center laboratory of UW-Madison neuroscientist Su-Chun Zhang, reveals the pervasive influence of Pax6 on the neuroectoderm, a structure that arises early in embryonic development and that churns out the two primary forms of brain cells -- neurons and glial cells -- and the hundreds of cell subtypes that make up the human brain.
"This is a well-known gene," says Zhang, a professor of anatomy in the UW School of Medicine and Pubic Health. "It's been known for a long time from work in mice and other animals, but what Pax6 does in human development isn't very well known."
In animals, the gene is known to play a role in the development of the eye and is seen in some neural cells. In the human cells used in the new Wisconsin study, Pax6 was observed in virtually all of the cells of the neuroectoderm. "The fact that Pax6 is uniformly expressed in all human neuroectoderm cells was a surprise," Zhang explains. "This is a phenomenon that is a departure from what we see in animals. It seems that in the earliest stages of development, human cells are regulated by different processes."
The finding may help explain why the human brain is larger and, in many respects, more advanced than what is observed in other species. In the laboratory dish, human brain stem cells are chock full of Pax6 and produce a large volume of cortical cells, notes Xiaoqing Zhang (no relation to Su-Chun Zhang), a UW-Madison neuroscientist and the lead author of the Cell Stem Cell paper.
"In human brain development, this plays a really important role," says Xiaoqing Zhang. "In humans, the cortex is a major part of the brain. In the mouse, the cortex is a much smaller part of the brain."
Adds Su-Chun Zhang, "In a way, it makes sense that the human brain is regulated in a different way. The brain distinguishes the human as a unique species."
In practical terms, the new finding will help scientists refine and improve techniques for making specific types of neural cells. Such cells will be critical for future research, developing new models for disease, and may one day be used in clinical settings to repair the damaged cells that cause such conditions as Parkinson's disease and amyotrophic lateral sclerosis or Lou Gehrig's disease.
"This gives us a precise and efficient way to guide stem cells to specific types of neural cells," says Xiaoqing Zhang. "We can activate this factor and convert stem cells to a particular fate."
The discovery of the new role of Pax6, says Su-Chun Zhang, is the first time researchers have discovered a single genetic factor in human cells that is responsible for shepherding blank slate stem cells to become a particular tissue stem cell type. "Until now, for any organ or tissues, we didn't know any determinant factors. This is the first," he says.
There are certainly other genes at play in the cells of the developing brain, says Su-Chun Zhang: "You may need additional genes, but they're in a supporting role. Pax6 is the key."
The National Institutes of Neurological Diseases and Stoke, part of the National Institutes of Health, supported the new study.
Cancer stem cells: Wnt — looking outside in
http://www.signaling-gateway.org/update/updates/201006/nrc2865.html
Alterations to lipid metabolism pathways might underlie the pathogenesis of several diseases, including cancer.
The Wnt signalling pathway drives stem cell self-renewal and is deregulated in most colon cancers; however, only a small proportion of colon cancer cells with Wnt-activating mutations have stem cell-like properties. Data from Medema and colleagues indicate that there is more to learn about the association between Wnt, stemness and the tumour microenvironment.
Using a reporter construct to assess Wnt activity, the authors found that only colon cancer cells with high Wnt activity exhibited stem cell properties, including the ability to form tumours when injected into nude mice. This increased activation of Wnt signalling was regulated by factors secreted from myofibroblasts in the stroma surrounding the colorectal tumours. When colon cancer stem cells were cultured with myofibroblasts, or treated with conditioned media derived from myofibro-blasts, their differentiation was prevented. The most abundant factor secreted by these cells is hepatocyte growth factor (HGF), which activates MET expressed by the tumour cells leading to the phosphorylation of AKT and glycogen synthase kinase-3ß. The authors also observed phosphorylation of ß-catenin on serine 522, which is associated with its stabilization and translocation to the nucleus — where it activates transcription of Wnt target genes. This enhanced transcriptional activity triggered by HGF was blocked by a specific MET inhibitor. Interestingly, cells with low Wnt activity and which showed no expression of stem cell markers and limited tumorigenic potential gained the ability to form tumours after treatment with HGF or when co-injected with myofibroblasts.
HGF is also secreted by myofibroblasts from human primary colon cancer samples, and analysis of such samples showed tumour cells with nuclear ß-catenin staining in close proximity to myofibroblasts.
These data provide evidence that myofibroblasts can establish and maintain stem cell properties in colon cancer cells through the regulation of Wnt signalling. They also suggest a strategy for targeting the self-renewal of cancer stem cells — blocking their interaction with the tumour microenvironment.
Teresa Villanueva
References
Vermeulen, L. et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature Cell Biol. 12, 468–476 (2010) | Article |
New Culture Dish Could Advance Human Embryonic Stem Cell Research
ScienceDaily (June 2, 2010) — A new synthetic Petri dish coating could overcome a major challenge to the advancement of human embryonic stem cell research, say University of Michigan researchers.
Under today's regulations, current stem cell lines have limitations in yielding human therapies because the cells have been grown on animal-based substances that don't behave in predictable ways.
"These nondefined, animal-based components create issues with the FDA (the U.S. Food and Drug Administration) and hinder clinical applications," said Joerg Lahann, associate professor of chemical engineering.
Lahann and Gary Smith, an associate professor in obstetrics and gynecology in the U-M Health System, and their co-workers built a new stem cell growth matrix that is completely synthetic and doesn't contaminate the stem cells with foreign substances that could interfere with their normal function.
A paper on the research was published online this week in Nature Biotechnology.
Today's most commonly used matrices are mouse embryonic fibroblast cells and Matrigel, which is made from mouse tumors.
"The problem is that the mouse-derived cells have batch-to-batch variability, and they secrete factors that nobody really understands. Stem cells are very sensitive to their environment," Lahann said.
The unknown factors hamper researchers' attempts to pinpoint how and under what conditions stem cells differentiate -- questions paramount to the development of future stem cell therapies.
The team tested six different polymer coatings and found that a water-soluble gel with the acronym PMEDSAH performed well when attached to the Petri dish even after 25 rounds of harvesting stem cells to grow new colonies.
"We have designed a fully synthetic, fully chemically defined hydrogel that has long-term stability and no batch-to-batch variability," Smith said. "Moreover, we have established that it can be used for long-term growth of human embryonic stem cells while maintaining all of their known normal functions.
"These include normal genetic makeup, lack of spontaneous differentiation and maintenance of pluripotency, which means they can still become any cell type of the human body. This is a perfect example of an interdisciplinary collaboration leading to information gained and future discovery of cures and improvements of human health."
Smith is also an associate professor in the departments of Molecular and Integrative Physiology and Urology, as well as director of the Reproductive Sciences Program. Lahann is also an associate professor in the departments of Materials Science and Engineering and Biomedical Engineering.
This research is funded by the National Science Foundation and the National Institutes of Health. The university is pursuing patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market.
New source of stem cells form heart muscle cells, repair damage
http://www.physorg.com/news194287667.html
May 28, 2010 A new and non-controversial source of stem cells can form heart muscle cells and help repair heart damage, according to results of preliminary lab tests reported in Circulation Research: Journal of the American Heart Association.
Mitral Valve Replacement - Minimally-Invasive Robotic Surgery Saint Joseph's Hospital of Atlanta - www.StJosephsAtlanta.org
Investigators in Japan used the amniotic membrane — the inner lining of the sac in which an embryo develops — to obtain stem cells called human amniotic membrane-derived mesenchymal (undifferentiated) cells (hAMCs).
"The amniotic membrane is medical waste that could be collected and used after delivery," said Shunichiro Miyoshi, M.D., Ph.D., co-author of the study and assistant professor in the cardiology department and Institute for Advanced Cardiac Therapeutics at the Keio University School of Medicine in Tokyo.
In laboratory studies, the hAMCs: transformed into heart muscle cells, with 33 percent beating spontaneously.
* improved function of rat hearts 34 percent to 39 percent when injected two weeks after a heart attack, while untreated hearts continued to decline in function.
* decreased the scarred area of damaged rat hearts 13 percent to 18 percent when injected after a heart attack.
* survived for more than four weeks in the rat heart without being rejected by the recipient's immune system, even without immunosuppressive medication.
The ability of hAMCs to convert into heart muscle cells was far greater than that from mesenchymal cells derived from bone marrow or fat, Miyoshi said.
That the implanted cells were not rejected is likely because the amniotic sac is a barrier between a woman and her developing fetus. To help prevent either of their immune systems from attacking the other as foreign tissue, the amniotic membrane between them does not produce the proteins that immune systems use to identify foreign tissue. This means the usual tissue-type matching (HLA typing) needed prior to transplantation would not be needed if hAMCs were used. Drugs to suppress the immune system also might not be needed after transplant.
The findings also suggest that hAMCs can differentiate into cells of various organs.
"If we had to create a cell bank system to cover every HLA type, we would need to store a great amount of cells, many of which would never be used," Miyoshi said. "Because hAMCs do not require such a system, it would be less expensive and usable for all patients."
Much work remains to be done before testing hAMCs in humans, said the researchers, who are repeating their experiments in larger animals and working to boost the number of heart cells generated by the hAMCs.
The investigators "are to be congratulated for their careful work that has brought forward a cell type that may offer the real potential for off-the-shelf cardiac myocyte [muscle cell]-based therapy," Marc S. Penn, M.D., Ph.D., and Maritza E. Mayorga, Ph.D., of the Cleveland Clinic, wrote in an editorial in Circulation Research.
Healing a Broken Heart With Stem Cells?
ScienceDaily (Apr. 12, 2010) — Some patients with heart muscles seriously affected by coronary heart disease may soon be able to benefit from an innovative treatment.
http://www.sciencedaily.com/releases/2010/04/100412095540.htm
Researchers at the Research Centre of the Centre hospitalier de l'Université de Montréal (CRCHUM), in collaboration with the Maisonneuve-Rosemont Hospital (MRH) are evaluating the safety, feasibility and efficacy of injecting stem cells into the hearts of patients while they are undergoing coronary bypass surgery.
These stem cells could improve healing of the heart and its function.
The IMPACT-CABG (implantation of autologous CD133+ stem cells in patients undergoing coronary artery bypass grafting) protocol evaluates this experimental procedure, which is destined for patients suffering from ischemic heart disease, in which the blood supply to the heart is decreased and associated with heart failure. These patients undergo open-heart coronary bypass surgery, performed by the medical team to improve perfusion of the heart muscle. A few weeks ago, the first patient received progenitor CD133+ stem cells isolated from his bone marrow and enriched at the Cell Therapy Laboratory of the MRH, and has been doing very well ever since. Already, improvement has been noted in the contraction capacity of his heart, which has improved its ability to pump blood.
Objective of the intervention
The IMPACT-CABG study targets a group of patients who suffer heart muscle failure due to coronary heart disease. The goal is to add another treatment option to coronary bypass to promote healing and regeneration of the damaged heart muscle. This new procedure is less invasive and less expensive than heart transplant, the only treatment now available for patients with severe heart failure. The researchers plan to recruit a total of 20 patients throughout Québec in the first phase. A second Canadian centre, at the General Hospital of the University of Toronto, will also take part in the trial. In 2007, the CRCHUM, in collaboration with the MRH, began the COMPARE-AMI clinical trial, to evaluate the safety and feasibility of intramyocardial injection of stem cells (injecting them into the heart through a catheter) in a different group of patients who have suffered their first infarction.
Before the IMPACT-CABG trial, previous studies in other countries had also evaluated the safety and feasibility of injecting different stem cells in the hearts of patients with cardiac dysfunction. This is a first study in Canada evaluating intramyocardial injection of stem cells. "Also, no research team in the country had implemented such a complete treatment process, going from harvesting stem cells in the patient, treating them, and injecting them directly into the myocardium," states Dr. Nicolas Noiseux, cardiac surgeon at the CHUM and principal investigator in the study.
To prepare for the intervention, cells from the bone marrow harvested at the CHUM are transferred to the cell therapy laboratory of the MRH to isolate the most immature stem cells, which will be injected directly into the patient's heart.
The IMPACT-CABG protocol research team is composed of the following CRCHUM investigators and professors from the Université de Montréal's Faculty of Medicine: Drs. Nicolas Noiseux, Samer Mansour, and Louis-Mathieu Stevens, and from HMR, Dr. Denis-Claude Roy.
This research protocol was made possible through a collaboration of the CRCHUM, the Maisonneuve-Rosemont Hospital's Cell Therapy Laboratory, Miltenyi Biotech, the CHUM's Cardiology and Cardiac Surgery Services, the Radiology Department, Health Canada and the Fonds de la recherche en santé du Québec.
Entest BioMedical Announces Creation of Proprietary Adult Stem Cell Lines
http://ih.advfn.com/p.php?pid=nmona&cb=1268054314&article=41869708&symbol=NB%5EENTB
SAN DIEGO, CA -- (Marketwire)03/08/10
Entest BioMedical Inc. (OTCBB: ENTB) announced today the creation of 3 bone marrow derived stem cell lines useful for optimizing laser intensities and wavelengths in laser enhanced stem cell therapy. A stem cell line is a defined cell population that is derived from a single cell and has the capability to replicate for long periods of time in vitro. Proprietary stem cell lines are commonly licensed for various applications ranging from research to product development.
The Company believes the development of these stem cell lines will assist in the progress of its stem cell therapy for COPD treatment.
These cells, ENT-CL101, ENT-CL221, and ENT-CL303, similar in nature to mesenchymal stem cells, are stable in cell culture, and can be expanded en masse for wide-scale screening.
"The creation of a standardized platform for assessing light-based therapies in vitro allows for mass screening for specific biological properties in the same way that drug companies screen small molecules," said Dr. Feng Lin, Director of Research and Development. "This is unique not only in the fact that we are using lasers instead of drugs for screening, but also that the targets are stem cell lines. The cell lines we have developed are also potentially useful for Pharmaceutical companies to screen agents that activate stem cells."
The traditional model of drug discovery involves screening thousands to millions of compounds in vitro on cells that represent the disease state. For example, if one is developing cancer therapeutics, the cancer cells are treated with random compounds and the compounds that kill the cells in vitro are chosen for animal testing. The creation of ENT-CL101, ENT-CL221, and ENT-CL303 allows for the same approach to be used in the area of light therapy. To date identification of appropriate frequencies and intensities for therapy is based on direct testing in animals, which is extremely costly.
The platform developed by Entest is anticipated to substantially save the cost of therapeutics development in the area of regenerative photoceuticals.
"We are extremely proud of the out of the box approach that our scientists have developed, which basically takes the area of laser-based therapy into the 21st Century drug development arena," said David Koos, Chairman and CEO of Entest.
About Entest BioMedical Inc.:
Entest BioMedical Inc. (OTCBB: ENTB) is involved with the development of stem cell therapy treatments for Chronic Obstructive Pulmonary Disease (COPD), immuno-cancer therapies, testing procedures for diabetes, stem cell research applications for diabetes and other illnesses. The Company also is involved with medical device development (including stem cell extraction instrumentation). ENT - 576? is a proprietary laser device currently under development by Entest. The Company has filed 3 patent applications relating to the treatment of COPD. Entest Biomedical Inc. is a majority owned subsidiary of Bio-Matrix Scientific Group Inc. (OTCBB: BMSN). Recently Entest published in the peer reviewed literature its platform technology, which is available at http://www.translational-medicine.com/content/pdf/1479-5876-7-106.pdf.
NIH may allow stem-cell lines from younger embryos
Lines derived from pre-blastocyst stage embryos could be eligible for agency funding.
http://www.nature.com/news/2010/100222/full/news.2010.85.html
Published online 22 February 2010 | Nature | doi:10.1038/news.2010.85
Meredith Wadman
The NIH may allow more stem cell lines to be eligible for federal funding. Clay Glennon, University of Wisconsin-MadisonThe US National Institutes of Health (NIH) is proposing to extend the human embryonic stem cell (human ES cell) lines eligible for federal funding to include those from earlier-stage embryos than currently allowed.
In an online notice on 19 February, the agency proposed revising its definition of fundable human ES cell lines to include lines derived from embryos "up to and including the blastocyst stage". By contrast, the current guidelines, published last summer, define human ES cells as cells derived from "the inner cell mass of blastocyst stage human embryos".
The proposed change to the rules will be out for public consultation for 30 days from 23 February, when it is formally published in the Federal Register, which publishes government notices.
Talking to Nature, Lana Skirboll, who directs the NIH's Office of Science Policy, describes the change as a "small technical revision". Because of the NIH's commitment to being transparent, she said, "If we were going to change a comma in the guidelines we might put out a Federal Register notice."
"From a scientific and ethical point of view," she adds, there's "no reason" to exclude lines derived earlier in embryonic development.
Skirboll says the issue came to the agency's attention after Advanced Cell Technology, based in Worcester, Massachusetts, recently submitted for NIH approval five lines derived from blastomeres — single cells removed from morulas (which are embryos a few days old that have not yet become blastocysts). Details of the cell lines were published in 2008 in Cell Stem Cell1.
Lining up
The company's stem-cell lines, Skirboll says, prompted the NIH to pore over its registry of already-approved lines. In the process, officials discovered that three lines also derived from pre-blastocyst embryos had already been approved from George Daley's lab at the Children's Hospital Boston. "We are going to take those lines and put them on hold," Skirboll says, so they will be unavailable for federally funded projects while NIH completes the formal revision of the guidelines.
Daley told Nature that the current definition is "too narrow" and that "ultimately, the correction will give access to more lines".
The proposed revision "may seem like a minor technical change, but is hugely important," says Robert Lanza, Advanced Cell Technology's chief scientific officer. "Human embryonic stem cells have been derived from morula-stage embryos in many, many papers."
Susan Fisher, a stem-cell biologist at the University of California, San Francisco, says that she has submitted ten lines derived from pre-blastocyst embryos to the NIH recently and the agency had come back to her with extensive questions. "I am super happy to see them take this issue on," Fisher says. "We obviously have a lot at stake." It is "a trivial, small change of the wording," she adds, "that could have enormous scientific benefit".
Lanza says that his company finds that several of its blastomere-derived lines were more versatile and robust than many others derived from later-stage embryos. "We have generated dozens and dozens of lines and there's no question that these are the lines we want to use."
Skirboll says that the agency plans to analyze the comments as they come in from 23 February and then "move pretty quickly" to finalize an amended definition.
References
Chung, Y. et al. Cell Stem Cell 2, 113-117 (2008).
PL1
Induced Pluripotent Stem Cells From Patients With a Premature Aging Disorder Bring Surprises
http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel607.html
Genetic reprogramming helps telomeres elongate--with implications for stem cell, aging and cancer research
Boston, Mass. February 17, 2010 -- In a study that ties stem cell research together with research on aging and cancer, investigators at Children's Hospital Boston have used genetic reprogramming to create cells from patients with a rare premature-aging disorder that are able to rebuild their telomeres--the tips of chromosomes that must be maintained to prevent a cell from "aging" and enabling it to divide and make copies of itself.
Publishing in Nature (Advance Online) on February 17, researchers in the laboratory of George Q. Daley, MD, PhD, Director of the Stem Cell Transplantation Program at Children's, report successfully reactivating the cellular enzyme telomerase, which maintains the telomeres, in patients with dyskeratosis congenita. In this rare genetic disorder, genetic mutations cause telomerase to be defective, leaving the chromosomes without protection from damage and unable to compensate for the natural shortening of telomeres that occurs when a cell divides. As a result, a patient's cells "age" more quickly, leading to bone-marrow failure (an inability to make enough blood cells), degradation of multiple tissues, premature aging-like symptoms and a much-shortened lifespan.
The findings suggest the possibility of developing drugs to help patients with dyskeratosis congenita maintain their telomeres, prolonging their lives. But the study also has broad implications for stem-cell research, as well as research on aging and even cancer.
"This paper illustrates how reprogramming a patient's skin cells into stem cells can teach us surprising lessons about human disease," says Daley, who is also associate director of the Stem Cell Program at Children's and a Howard Hughes Medical Institute investigator.
The ability to maintain and elongate telomeres is believed to endow stem cells with the ability to endlessly replicate themselves. Researchers studying aging believe that this same ability could slow or halt natural aging, at least in our cells. In the cancer field, telomerase is thought to contribute to the "immortalization" and uncontrolled growth of cells that marks human cancer, and has become a target in attempts to treat cancer.
The research project, led by Suneet Agarwal, MD, PhD, took skin cells from three patients with dyskeratosis congenita and introduced four genes into the cells to transform them into pluripotent stem cells (iPS cells), which are similar to embryonic stem cells. Their goal was to better understand the disease at the cellular level--and also to see if the process of genetic reprogramming would actually affect the disease.
It did. Once reprogrammed, the diseased cells showed increased levels of telomerase RNA component (TERC), the part of the telomerase enzyme that provides the template for adding DNA onto the telomeres. Even though the patients had a genetic defect in TERC, the telomeres were once again able to elongate, and the cells were able to replicate indefinitely - just as healthy iPS cells can.
Further studies showed that human embryonic stem (ES) cells maintain elevated TERC levels similar to those found in iPS cells derived from healthy people, and that the more TERC found in iPS cells from patients with dyskeratosis congenita, the more telomerase activity.
The discovery of telomerase, in the 1980s, won the 2009 Nobel Prize in Medicine and Physiology. Since then, researchers have focused largely on a different component of the enzyme, known as TERT, which is the portion of the enzyme that actually adds DNA to the telomeres. But the RNA component, TERC, turns out to be equally important in telomere maintenance.
"This study suggests that the level of TERC isn't just static, but could possibly be manipulated," says Agarwal, an attending physician in Children's Stem Cell Transplantation Program. "If you could do that in a patient with dyskeratosis congenita, you might be able to elongate their telomeres and sustain them a little longer."
Agarwal is seeking funding to do drug screening to identify compounds that up-regulate TERC. In addition, if iPS cells could be made from these patients, their TERC deficiency could be corrected through the reprogramming process itself--without the need for gene therapy to replace the defective TERC gene. Since dyskeratosis congenita is a blood disorder, these iPS cells could then be used to create blood stem cells for transplantation that would be compatible with patients' immune systems.
"If you give patients with dyskeratosis congenita a conventional bone marrow transplant, they tend to have higher mortality than other patients because their disease affects so many organ systems," says Agarwal. "For these patients, and for patients with other bone marrow failure syndromes, it would be ideal to give them a gentler stem cell transplant from their own cells."
Since creating iPS cells seems to promote telomere elongation, the study also suggests that people of all ages could potentially benefit from cell therapies derived from iPS cells, Agarwal says. "We're not saying we've found the fountain of youth, but the process of creating iPS cells recapitulates some of the biology that our species uses to rejuvenate itself in each generation," he says.
The study also has implications for understanding cancer. Patients with dyskeratosis congenita are predisposed to cancer, because their shortened telomeres expose their DNA to cancerous mutations. But researchers have wondered why, if the telomeres are shortened, the cancers are able to proliferate. They speculate that cancer cells, which share some characteristics of stem cells, may be able to proliferate by up-regulating TERC.
The study was funded by the National Institutes of Health and the Manton Center for Orphan Disease Research.
Any opinions on which STEM cell companies have the better pipeline?
Or order of which more likeable than others?
The very same to you, and a Joyous Christmas & New Years to you and yours...
The LORD bless you and keep you; the LORD make his face shine upon you and be gracious to you; the LORD turn his face toward you and give you peace." Numbers 6:24-26
Numbers 6:24 : Yebarechecha HaShem veyishmerecha Numbers 6:25: Yaer HaShem panav eleicha Vihunekka Numbers 6:26: Yissa HaShem panav eleicha veyassem lecha shalom......Mark
HI There Precious~HAPPY HOLIDAYS and may GOD BLESS
Stem cells help cure blindness
By Clive Cookson, Science Editor
Financial Times December 22 2009 16:50
A stem cell treatment developed in Newcastle has restored good vision to eight people who had lost sight in one eye.
”This has transformed my life,” said one of the patients, Russell Turnbull, whose right eye was burned and scarred in an ammonia attack after intervening in a fight on a Newcastle bus 15 years ago. “I’m working, I can go jet skiing and also ride horses.”
The new technique – developed at the North East England Stem Cell Institute – involves taking a small biopsy from the cornea of the patient’s good eye and multiplying its stem cells several hundredfold in the lab with a special culture system. When the cells are transplanted back into the damaged eye, they restore the damaged cornea.
“The operation has improved the sight in my right eye from 10 per cent to 90 per cent,” said Mr Russell, 38, “and best of all it has removed the constant pain and light sensitivity in the eye.”
The technique could help thousands of people who suffer severely impaired vision through a condition known as Limbal Stem Cell Deficiency. This is caused by damage to the surface of the cornea, caused by disease, chemical burning or physical injury.
Sajjad Ahmad, the scientist who developed the Newcastle method, said its success showed the scope for using the patient’s own stem cells to treat the eye. Details are published in the journal Stem Cells.
But the technique depends at present on having one healthy eye from which to extract stem cells. And, while it might be extended to treat other disorders of the cornea, it is not suitable for retinal problems such as blindness caused by macular degeneration. Scientists elsewhere are planning clinical trials of stem cells derived from early human embryos to treat retinal disease.
The Medical Research Council has given the Newcastle team a £1.5m grant to extend the trial to 25 more patients over the next three years, said Francisco Figueiredo, consultant eye surgeon at the city’s Royal Victoria Infirmary.
“We want to take this from a research-based technique to one that could be used in eye departments throughout the NHS,” said Dr Ahmad. “It would save a lot of money as well as preventing suffering, because patients with LSCD currently have to see an eye specialist every six weeks or so.”
Copyright The Financial Times Limited 2009.
Pfizer Acquires a Stem-Cell Therapy
By ANDREW POLLACK
NYT December 21, 2009
Pfizer said Sunday that it was buying the rights to a somewhat controversial cell therapy from Athersys, a biotechnology company — a sign of big pharmaceutical companies’ growing interest in stem cells.
Pfizer will have the rights to develop Athersys’s cells to treat inflammatory bowel disease, the companies are expected to announce on Monday. It will pay Athersys $6 million initially and up to $105 million in the future.
The relatively small payment reflects that “it’s really early for cell therapy and there’s more research to be done,” said Ruth McKernan, chief scientific officer of Pfizer Regenerative Medicine, a unit created by the company about 18 months ago to develop treatments based on stem cells.
Athersys’s cells, derived from human bone marrow, have not yet been tested in people with inflammatory bowel disease, a term that encompasses ulcerative colitis and Crohn’s disease. But the product, called MultiStem, is in early human testing as a treatment for heart attacks and for cancer patients receiving bone marrow transplants.
Athersys, founded in 1995 and based in Cleveland, is publicly traded and still unprofitable. Its shares closed at $1 on Friday.
Stem cells can form different types of tissue in the body. Pfizer and Athersys envision the cells being infused into patients not to replace damaged tissue but rather to produce various proteins that would help existing tissues heal or prevent them from being damaged.
Stem cells derived from adult tissues, like MultiStem, are less ethically controversial than stem cells from human embryos. But MultiStem has been dogged by scientific controversy.
The cells were initially developed at the University of Minnesota, which said they were multipotent adult progenitor cells — almost as versatile as embryonic cells. But some scientists had trouble replicating those findings, and some papers published by the Minnesota researchers were retracted or corrected.
Dr. McKernan said that those controversies were “in the past now” and that scientists have been able to replicate the findings.
Big pharmaceutical companies have been cautious about stem cells because of the ethical controversies and the early stage of the research. Also, some cell-based therapies must be tailored to each patient, a departure from the business model of producing one-size-fits-all pills.
But as the science of stem cells has advanced, drug companies are taking an interest.
Pfizer is also developing a stem-cell treatment for macular degeneration, an eye disease, working with University College London. It is doing research with Novocell, a San Diego company trying to turn embryonic stem cells into insulin-producing cells to treat diabetes.
Novo Nordisk is working with Cellartis on stem-cell treatments for diabetes. Johnson & Johnson has invested in Novocell and Tengion, another regenerative medicine company. GlaxoSmithKline is providing $25 million to Harvard’s stem-cell institute. And Novartis and Roche have invested in Cellerix, a Spanish stem-cell company.
First Human Embryonic Stem Cell Lines Approved under New NIH Guidelines
http://www.genengnews.com/news/bnitem.aspx?name=69955197&source=genwire
NIH director, Francis S. Collins, M.D., Ph.D., today announced the approval of the first 13 human embryonic stem cell (hESC) lines for use in NIH-funded research under the recently adopted NIH Guidelines for Human Stem Cell Research.
“In accordance with the guidelines, these stem cell lines were derived from embryos that were donated under ethically sound, informed-consent processes,” points out Dr. Collins. “More lines are under review now, and we anticipate continuing to expand this list of responsibly derived lines eligible for NIH funding."
Children's Hospital Boston developed 11 of the approved lines, and The Rockefeller University in New York City developed the other two. An additional 96 lines have been submitted to NIH for either internal administrative review or consideration by the external Working Group for Human Embryonic Stem Cell Eligibility Review and the NIH Advisory Committee to the Director (ACD). The working group provides findings to the ACD, which makes recommendations to the NIH director, who decides whether the hESCs may be used in NIH-funded research and lists those deemed eligible on the NIH Human Embryonic Stem Cell Registry.
Over 30 NIH grants funded in the 2009 fiscal year, totaling more than $20 million, proposed to use hESCs; these grants have been restricted until approved lines became available on the NIH registry.
With today's announcement, these principal investigators may obtain registry-listed hESCs from the owners of the lines and proceed with their research. This group of grants includes research using hESCs for the therapeutic regeneration of diseased or damaged heart muscle cells, developing systems for the production of neural stem cells and different types of neurons from hESCs in culture, and developing a cell culture system for the large-scale production and self-renewal of hESCs.
In addition, a number of Challenge Grant applications, which could be funded through the American Recovery and Reinvestment Act in the 2010 fiscal year, proposed to use hESCs.
On March 9, President Obama issued Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The executive order stated that the secretary of the HHS, through the director of NIH, may support and conduct responsible, scientifically worthy human stem cell research including human embryonic stem cell research to the extent permitted by law.
The NIH Guidelines for Human Stem Cell Research, published on July 7, implement the executive order as it pertains to extramural NIH-funded stem cell research, establish policy and procedures under which the NIH will fund such research, and help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law.
The gold rush for induced pluripotent stem cells
http://www.nature.com/nbt/journal/v27/n11/full/nbt1109-977.html
Abstract
As the first commercial ventures are formed around induced pluripotent stem (iPS) cell research, who will have the freedom to operate commercially remains a big unknown. Sarah Webb reports.
Introduction
Induced pluripotent stem cells. Technology for producing iPS cells is developing quickly. (Image courtesy of James Thomson, University of Wisconsin Stem Cell and Regenerative Medicine Center)
Research on induced pluripotent stem (iPS) cells continues at a breathtaking pace. Not only is rapid progress being made in understanding the basic mechanisms of reprogramming, but also the first applications of this work are beginning to appear. In the past 18 months, iPS cells have been used to generate disease-specific cells for several disorders (mostly neurodegenerative, and a September issue of Nature describes the use of iPS cells derived from patients with familial dysautonomia to generate neurons to evaluate drug candidates4. That opportunity—to create cellular models of disease and then use them to screen for drug candidates—highlights the promise of this technology.
iPS cells offer a pathway to pluripotency unhindered by the ethical and practical obstacles associated with research using human embryos and human eggs. "Many of the pharmaceutical companies were really concerned about using ES [embryonic stem] cells," says Mahendra Rao, vice president of research in stem cells and regenerative medicine at Invitrogen, part of Life Technologies, in Carlsbad, California. "Now that they have an alternate to getting pluripotent cells it becomes an easier choice for them to begin work with iPS [cells]."
But many fundamental research questions about the reprogramming process (by which differentiated somatic cells are returned to an ES cell–like state) remain unanswered. And with no patents issued as yet, but a raft of reprogramming patents filed (75 and counting), intellectual property (IP) and future freedom to operate remain uncertain. Undeterred, companies in this space are crafting strategies to move forward, by targeting unmet scientific needs, filing patent applications and purchasing licenses to other IP, and building their knowledge base through in-house talent and strategic partnerships. At the same time, commercialization efforts are zeroing in on near-term goals—reprogramming kits, cell lines for toxicology screening and disease models (Table 1)—leaving therapies for later.
The new and the unknown
The initial technologies for producing iPS cells reported by Shinya Yamanaka of Kyoto University in Japan and the Gladstone Institute at the University of California, San Francisco, and James Thomson of the University of Wisconsin-Madison delivered four reprogramming genes with viral vectors. The presence of integrated vector sequences, however, is problematic, particularly for clinical application. For one thing, the potential for insertional oncogenesis exists. In addition, "vectors always have a basal expression level, you can't turn them off really," says Rudolf Jaenisch of the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology in Cambridge. That has spurred a search for chemicals that can moonlight for the reprogramming factors.
Already, researchers have been able to replace one or more of the reprogramming genes with small molecules or proteins. And as they look toward clinical applications of iPS cells, they're focusing on factors that can be added extracellularly to reprogram cells. In May, an international group of researchers reported reprogramming human fibroblasts with the four recombinant proteins alone5. And in October, Sheng Ding of Scripps Research Institute in La Jolla, California reported reprogramming human fibroblasts to iPS cells using three small molecules6. Combinations of small molecules with proteins are likely to be most efficient for reprogramming, Ding predicts.
However, the more challenging issue, according to Jaenisch, is the ability to differentiate iPS cells efficiently and predictably into the cell types wanted. Background vector expression could be preventing iPS cells from differentiating as efficiently as ES cells. Jaenisch's group has done experiments showing that iPS cells with only 1% background vector expression showed significantly different gene expression patterns compared with iPS daughter cells in which the vectors had been excised.
Epigenetic modifications, accumulated over a lifetime in donor somatic cells, are likely to play a role in the efficiency of reprogramming and subsequent differentiation. Differentiation is challenging even with ES cells, says Ed Baetge, CSO at Novocell in San Diego, because each line is genetically distinct, and culture conditions and other selective pressures can alter the state of chromatin or DNA methylation as the cells differentiate. "The problem with iPS cells is that they're more epigenetically variant depending on what source you make them from and how you reprogram them," he says. "You already have issues with [differentiating] ES cells, and you magnify them with iPS cells."
Another important issue, particularly for clinical applications, will be a better understanding of the molecular mechanisms of reprogramming. Why those four genes reprogram cells and another four genes don't is not fully understood, says Ian Ratcliffe, president and CEO of Stemgent in Cambridge, Massachusetts, and San Diego. Even if you're using proteins, or eventually small molecules, to reprogram cells, he says, "the FDA is likely to want to know what is the mechanism of action of these molecules if you want to put [these cells] into humans."
The murky waters of intellectual property
With advances in the field announced nearly weekly, numerous patent applications have been filed, but no patents have been issued in either the US or Europe. As a result, companies have freedom to operate within this space until the patent offices make those decisions. "You have the tension that this just looks like a really attractive technology to commercialize. Then you have the challenge that we're not clear on what we can patent or what we can't patent," says Ken Taymor, executive director of the Berkeley Center for Law, Business and the Economy in California.
The patent uncertainty centers around two critical questions, notes Rao. Will the patents be based on the process or the source? In one scenario, it's possible that early discoveries such as those by Yamanaka and Thomson could receive broad patents and all companies would need a license to use iPS cells. However, a broad patent seems unlikely, according to David Resnick, a patent attorney with Nixon Peabody in Boston, in part because of changes in the patent office since the broad ES cell patents of the 1990s. "There's concern in the patent office that they don't want to have such a broad patent that it would stop people from being able to make and use iPS cells," he says.
Because the original technology using viral vectors has already been supplanted, "we know that technology in itself is not commercializable," says Taymor. The more significant question, Taymor adds, "is where the line gets drawn subsequent to Yamanaka, what's patentable based on his disclosure." Taymor is currently analyzing 75 patent applications relating to reprogramming technology to assess that question. Claims related to methods are easier to show and are therefore more likely, notes Resnick. However, based on the recent history, "the latest and greatest method [for producing an iPS cell] seems to have a half-life of several months," he adds. With decisions likely a few years off, he says, it wouldn't be surprising if some technologies are obsolete before the patents are prosecuted.
"The IP landscape around induced pluripotent cells is just as complicated as the IP landscape around the rest of the field of regenerative medicine," according to Greg Bonfiglio of Proteus Venture Partners in Palo Alto, California. However, he suspects that the current uncertain and complex IP situation might not matter in the long run. "I think that this technology is advancing very, very rapidly, and with each advancement the technology moves forward and could be less dependent on earlier technology."
The second question is how the patent office might distinguish iPS cells from other pluripotent cells, Rao adds. This question becomes important when thinking about methods for differentiating pluripotent cell lines into specific cell types. The method for differentiating an iPS cell might be identical to that used with an ES cell. If so, patents already issued based on ES cell research might predominate. In addition, because of their age, some patents for that ES cell work may soon revert to the public domain.
Companies currently operating in this space are protecting themselves by licensing broadly. Reagents and tools company Stemgent is talking with researchers with relevant technologies and licensing technology in the research products area, says Ratcliffe. He estimates that his company has purchased more than 50 such licenses. In many cases those licenses are for patent claims, rather than issued patents.
"I think that this [IP] space is complicated enough that there will be many roads to roam," says Chris Kendrick-Parker, chief commercialization officer of Cellular Dynamics International (CDI) in Madison, Wisconsin. "We believe that there's going to be very little space for blocking." Although he believes his company has a strong IP position, he thinks their execution as a business will be more important in the long run than their IP.
The money trail
Current commercialization strategies are focused around producing research tools for making iPS cells and using iPS cells in drug discovery. In April, ArunA Biomedical, a privately held company in Athens, Georgia, specializing in stem cells, launched a kit for producing iPS cells using lentivirus vectors, which was co-developed with Open Biosystems, in Huntsville, Alabama (and a part of ThermoFisher, the instrument and reagent supplier). Stemgent provides a variety of reagents, media and tools for cellular reprogramming, growth and differentiation.
Companies with experience with human ES cells are looking at iPS cells alongside their work with ES cells. In December, Novocell announced a partnership with Shinya Yamanaka to explore the development of iPS cells to produce pancreatic islet cells as a complement to the company's existing work in this area with ES cells. Invitrogen is working to provide tools and reagents for both cell types, Rao says. "If we have the best tools for ES cells, those tools should be good for iPS as well."
Collaboration as a catalyst
But for companies focused primarily on iPS cells, moving forward from reagents and kits toward cell lines and disease models in the commercial space has involved bringing together scientific know-how, funding sources and partners from academia or industry. "[Research is] just in its nascent period. In the current economic climate it's hard to get money to do big research projects in this space. People want products," Ratcliffe says.
One such undertaking is a consortium announced in May between Stemgent and Boston-based Fate Therapeutics, a private drug discovery company founded by Jaenisch, among other luminaries in stem cell field. The consortium, named Catalyst, brings together Stemgent's growing catalog of reagents with Fate Therapeutics' research into stem cell–based therapeutics and provides access to both products and knowledge base to a select group of clients.
"We believe there are a lot of precompetitive technologies," says Ratcliffe of Stemgent. "The pharmaceutical and biotech companies want the same sorts of tools and would like to see them validated in a number of different ways." Such tools could include iPS cell–generated disease models or alternatively normal iPS cells differentiated into different lines for toxicology screening. With an initial investment of a few million dollars, partners would provide the funding to support the research, says Paul Grayson, president and CEO of Fate Therapeutics. In return, they receive a license to the existing IP portfolio and the technology that results from Catalyst. No pharmaceutical companies have signed on yet.
All of the Catalyst funds will go directly into research, Grayson adds. Pharmaceutical partners will maintain rights to drug discoveries that they make using the common technology platform, but any improvements to the platform will be shared among Catalyst members, says Scott Wolchko, Fate's CFO. "So we are a developer of the technology but also an end-user of the technology," he says. Nonprofits and academic researchers would be able to license the Catalyst technology for free. "I believe that we as a company have a lot more to gain by pushing our technology into the academic market than by keeping those [inventions] internally," says Grayson.
Focusing on disease models
Another collaboration led to the creation of iPierian, formed in July through the merger of S. San Francisco–based iZumi Bio, an iPS-cell drug discovery company, and Pierian. The new company is focused on using iPS cells to develop small molecules and biologics against neurodegenerative diseases. Pierian's founders, Harvard University professors George Daley, Douglas Melton and Lee Rubin, are all on the scientific advisory board of the new company. In addition, the company has hired young scientists such as John Dimos, a former postdoc in Kevin Eggan's group at the Harvard Stem Cell Institute and lead author on their Science paper that demonstrated the differentiation of iPS cell–based motor neurons from patients with ALS2. The company is also collaborating with Shinya Yamanaka on other methods for generating iPS cells.
iPierian CEO John Walker emphasizes that the company will not be marketing research tools. Rather, the company will be focused on drug discovery applications. By developing cellular models from patients, they plan to use those cells to both better understand the disease and investigate novel pathways and novel targets to intervene in the disease, says chief technology officer Berta Strulovici.
Although iPierian is not currently looking toward the therapeutic applications of iPS cell–derived cells, the company hasn't ruled it out.
The proof is in the cardiomyocytes
CDI was formed to industrialize both the process of reprogramming somatic cells to form iPS cells and the differentiation of those cells into useful cell types for toxicology screens and drug discovery. The company produces billions of iPS cells each day using the plasmid-based method developed by founder Jamie Thomson with recent hire Junying Yu7, and according to Kendrick-Parker, is producing cardiomyocytes for pharmaceutical companies, including Roche's Palo Alto, California, research facility. In the past few months, CDI has also announced exclusive licensing agreements with both Mount Sinai School of Medicine in New York and Indiana University–Purdue University Indianapolis for technology related to differentiation of cardiomyocyte progenitor cells and methods for producing highly purified cardiomyocytes.
"There really is an unmet need for models to understand cardiotoxicity," says Kendrick-Parker. Several drugs have made it to the market that have cardiotoxic profiles and that's unacceptable." These cells have the added bonus of a physiological function that researchers can monitor—a 'heartbeat'—in addition to other biochemical cues. In September CDI and VivoMedica, a Sittingbourne, UK, pharmaceutical technology company, launched CARDIOTOX, a consortium that will use CDI's cardiomyocytes in VivoMedica's microelectrode arrays and data analysis techniques. The consortium will include a group of pharmaceutical partners, who will validate the system as a screening tool to predict the cardiac proarrhythmic potential in new drug candidates. This type of feedback from pharmaceutical companies is valuable, Kendrick-Parker says, because rather than looking at standard cell biology markers, CDI gets information on how the cardiomyocytes perform compared with existing model systems. "A lot of people can make cardiomyocytes, but the key thing is, do those cells respond to therapeutics or drugs in a way that's expected?" he says. Consistency in that response is what will give pharmaceutical companies confidence that a tool will fit their needs, he says. In December CDI will launch iCell cardiomyocytes, a commercially available kit that will include cryopreserved cells, media and other tools.
Although Kendrick-Parker is excited about the opportunity that iPS cells provide to produce cell types with varying genetic profiles for drug development, CDI isn't looking toward future commercial cell therapies. Instead, he says, "we believe that we look like a great partner, for either pharmaceutical companies as they start to evolve toward these types of applications from a therapeutics perspective, as well as any other entity who has ideas about differentiation and cell therapy potential."
iPS cells and pharma
Large pharmaceutical companies are also beginning to explore the iPS cell space. London-based GlaxoSmithKline and the Harvard Stem Cell Institute announced a 5-year, $25 million collaboration in July 2008 that would provide tools from stem cells including human ES cells and iPS cells for drug discovery. Four months later, New York–based Pfizer launched its Regenerative Medicine group. Although the safety group at Pfizer is also looking at iPS–derived cell lines for toxicology studies, the regenerative medicine group is specifically focused on drug discovery using cell lines derived from iPS and hES cells. One particular area of interest is in neurodegenerative diseases, such as ALS and Huntingdon's disease, says CSO Ruth McKernan.
The unit already has a publicized collaboration with Novocell focused on using Pfizer's library of small molecules toward the differentiation of human ES cells into pancreatic beta cells.
But as with other companies entering this area, Pfizer sees itself as focusing on collaborative opportunities. "When we entered this space, we did so with the expectation that we would do a lot by collaboration because there are so many good academic and biotech groups out there," McKernan says. "We want to partner so that we can get right at the very front of science as quickly as possible."
The speed with which the science is progressing characterizes all aspects of iPS cell research. Whereas most fields develop over years or even decades, the explosion in iPS technology has developed "right before our eyes," says Resnick. "It's intriguing from a scientific and from a legal point of view."
That pace of development seems unlikely to slow any time soon. The promise of the field, for drug discovery or even personalized medicine, without the barriers associated with research with embryos or human eggs, has attracted talented people, Bonfiglio says. "You can't underestimate the power of that intellectual capital, and it's helped move the field along."
))PL1((
Amazing Success in first of the first trial participants...
Pluristem Therapeutics Inc. (NasdaqCM:PSTI) (DAX:PJT) today announced that safety and potential efficacy parameters were demonstrated by the three month follow up data from the first patient ever to receive its placenta derived cell therapy product, PLX-PAD. The patient is participating in a Phase I dose-escalating clinical trial in Europe with PLX-PAD, the company’s leading product candidate for the treatment of critical limb ischemia (CLI), the end-stage of peripheral artery disease (PAD).
The first patient was treated with the lowest of three doses and has completed the three month follow up with the following results:
•The patient’s Rutherford Category (a scale of the severity of a patient’s limb ischemia) decreased by 50 percent.
•The patient has reported that the ability to walk pain free increased from 20 meters (approximately 60 feet) to 120 meters (approximately 360 feet), representing a 500 percent improvement over baseline.
In addition, the patient’s VascuQol score (quality of life score), VAS score (pain score), and the hemodynamic parameters, ankle-brachial index, toe-brachial index, and transcutaneous oxygen pressure, improved compared to baseline.
Based on the decrease in the patient’s Rutherford Category, Pluristem believes that the patient may no longer fulfill the criteria for the diagnosis of critical limb ischemia.
Professor Doctor André Schmidt-Lucke, Director of the Franziskus-Krankenhaus Institute of Berlin, Germany and Project Leader of the PLX-PAD clinical trial stated, "Although we are early in the clinical trial, Pluristem’s PLX-PAD product could represent a significant advancement towards finding an efficacious therapy for critical limb ischemia.”
"These results are the first indication of the safety and efficacy of the treatment with PLX-PAD,” said Zami Aberman, chairman and CEO of Pluristem. "Although these results may not be entirely reproducible in other patients, we are encouraged that the first patient ever to receive our PLX-PAD cells in the lowest of the three doses has exhibited data to suggest our product candidate is safe and potentially efficacious.”
Jaw bone created from stem cells
http://news.bbc.co.uk/2/hi/health/8290138.stm
Scientists have created part of the jaw joint in the lab using human adult stem cells.
They say it is the first time a complex, anatomically-sized bone has been accurately created in this way.
It is hoped the technique could be used not only to treat disorders of the specific joint, but more widely to correct problems with other bones too.
The Columbia University study appears in Proceedings of the National Academy of Sciences.
The bone which has been created in the lab is known as the temporomandibular joint (TMJ).
“ The availability of personalized bone grafts engineered from the patient's own stem cells would revolutionise the way we currently treat these defects ” Dr Gordana Vunjak-Novakovic Columbia University
Problems with the joint can be the result of birth defects, arthritis or injury.
Although they are widespread, treatment can be difficult.
The joint has a complex structure which makes it difficult to repair by using grafts from bones elsewhere in the body.
The latest study used human stem cells taken from bone marrow.
These were seeded into a tissue scaffold, formed into the precise shape of the human jaw bone by using digital images from a patient.
The cells were then cultured using a specially-designed bioreactor which was able to infuse the growing tissue with exactly the level of nutrients found during natural bone development.
Big potential
Lead researcher Dr Gordana Vunjak-Novakovic said: "The availability of personalised bone grafts engineered from the patient's own stem cells would revolutionise the way we currently treat these defects."
Dr Vunjak-Novakovic said the new technique could also be applied to other bones in the head and neck, including skull bones and cheek bones, which are similarly difficult to graft.
The option to engineer anatomically pieces of human bone in this way could potentially transform the ability to carry out reconstruction work, for instance following serious injury or cancer treatment.
She said: "We thought the jawbone would be the most rigorous test of our technique; if you can make this, you can make any shape."
She stressed that the joint created in the lab was bone only, and did not include other tissue, such as cartilage. However, the Columbia team is working on a new method for engineering hybrid grafts including bone and cartilage.
Another major challenge for scientists will be to find a way to engineer bone with a blood supply that can be easily connected to the blood supply of the host.
Professor Anthony Hollander, a tissue engineering expert from the University of Bristol who helped produce an artificial windpipe last year, said there was still a lot of work to be done before the new bone could be used on patients.
But he said: "One of the major problems facing scientists in this field is how to engineer a piece of bone with the right dimensions - that is critical for some of these bone defects.
"This is a lovely piece of tissue engineering which has produced bone with a high degree of accuracy in terms of shape."
Posted by: mick Date: Monday, September 14, 2009 6:53:18 AM
In reply to: afxm who wrote msg# 895 Post # of 901
Leukemia, stem cell scientists, N.Y. mayor get Lasker Awards
Updated 11h 51m ago | Comment | Recommend
http://www.usatoday.com/news/health/2009-09-14-lasker-awards_N.htm?csp=24&RM_Exclude=Juno
By Elizabeth Weise, USA TODAY
One of the most prestigious prizes in medicine is being awarded this year to scientists working on stem cells and leukemia — and to New York's mayor for his fight to cut tobacco use.
The Lasker Awards, which are announced today, have been given since 1945. They recognize the contributions of scientists, physicians and public servants internationally working to cure, treat and prevent disease.
"It's right up there with the Nobel Prize," says Gary Sieck, a research director at the Mayo Clinic, Rochester, Minn. "The people who get it are at the top."
The Lasker-DeBakey Clinical Medical Research Award goes to three scientists whose turned a fatal cancer, myeloid leukemia, into a manageable condition with their discovery of the drug Gleevec (imatinib mesylate).
Brian Druker, 54, of Oregon Health & Science University, Nicholas Lydon, 52, formerly of the Novartis pharmaceutical company, and Charles Sawyers, 50, of Memorial Sloan-Kettering Cancer Center did the work in the 1990s. The drug inhibits the protein made by an abnormal gene that causes this form of leukemia. Further research was able to stop resistance to the drug in some patients.
When the first results of preliminary tests came in, in 1999, "almost everyone had some form of response, either a complete or partial remission. In a Phase 1 study you never see that," says Sawyers. "Now it seems like such a logical approach, but at the time it had never been done."
Being awarded the prize is "an incredible badge of respect and honor," he says.
The Lasker Basic Medical Research Award goes to John Gurdon, 76, of Cambridge University and Shinya Yamanaka, 47, of Kyoto University and San Francisco's Gladstone Institute of Cardiovascular Disease. Their work has helped pave the way for the possibility of made-to-order stem cell treatments for individual patients.
Gurdon began working with frog eggs in the 1950s and was the first to successfully clone a frog, in the 1960s. This led directly to the cloning of mammals in the 1990s.
Yamanaka's ground-breaking announcement in 2006 that he had successfully reprogrammed a mouse skin cell to turn into stem cells holds promise for creating stem cells without destroying an embryo, up until now a major ethical and legal hurdle.
The Mary Woodard Lasker Public Service Award goes to New York Mayor Michael Bloomberg, 67, who waged an effective campaign to get people in his city to stop smoking and start eating better.
The Lasker Awards come with a prize of $250,000 in each category. They are sometimes called "America's Nobels," in part because 76 Lasker laureates have gone on to receive the Nobel Prize.
"MultiCell Technologies is Granted U.S. Patent"
http://ih.advfn.com/p.php?pid=nmona&cb=1250785000&article=39123853&symbol=NB%5EMCET
"Cancer Advance Identifies Drug to Destroy Powerful Stem Cells"
Posted by Mick on the STEM board.
By Rob Waters
Aug. 14 (Bloomberg) -- Scientists said they have found a drug compound that attacks in a new way the stem cells that fuel tumor growth, opening a path to a new type of anti-cancer treatment.
The compound, salinomycin, reduced the number of cancer stem cells 100 times more than did Bristol-Myers Squibb Co.’s Taxol, a common chemotherapy medicine, according to a report published yesterday in the journal Cell.
The idea that a small group of stem cells drives tumor growth while resisting chemotherapy has been documented by researchers for more than a decade. Scientists at Massachusetts Institute of Technology and the Broad Institute bolstered the theory by showing that the proportion of stem cells in a tumor rose after treatment with standard therapy and declined dramatically with salinomycin.
“It’s exactly the opposite of standard treatment,” said Max Wicha, director of the University of Michigan Comprehensive Cancer Center. “While chemotherapy kills the bulk of cells in a tumor and leaves the cancer stem cells behind, this new treatment does the opposite -- it actually targets and kills the cancer stem cells.”
Wicha, who has developed ways of identifying cancer stem cells, wasn’t involved in yesterday’s study, which he called a “very important” finding.
“This is telling us that cancer stem cells are not going to be resistant to everything,” Wicha said. “It tells us it’s going to be possible to develop specific compounds that can target this cell population.”
New Path to Drugs
The MIT and Broad researchers will conduct further testing of salinomycin in animals to assess its potential to treat humans, said Piyush Gupta, a researcher at the Cambridge, Massachusetts-based Broad Institute and co-author of the study. While the outcome of that research is unknown, the work pinpoints a new way to find effective drugs, he said.
“We now have a method that researchers anywhere in the world can use to find agents that can kill cancer stem cells and potentially treat cancer,” Gupta said yesterday in a telephone interview.
The strategy of finding and attacking these cells results from pioneering work by John Dick, a University of Toronto scientist who in 1997 showed that certain cells in leukemia propelled the growth of new cancer cells. In 2007, he identified similar cells in colon cancer.
Stem cells, for reasons not yet known, appear to fuel the growth of several kinds of cancer including breast, lung and brain tumors, according to studies done in recent years. The cells are resistant to standard cancer therapy, so finding a way to thwart them is important, said Judy Lieberman, a professor of pediatrics at the Immune Disease Institute at Harvard Medical School.
‘These Are the Cells’
“These are the cells that are the important cells and if you don’t eliminate them, the tumors can grow back and recur,” Lieberman said yesterday in a telephone interview. “Any way you can figure out to specifically target the cancer stem cells is going to fill an important gap in the therapies we have at hand.”
Scientists at universities and biotechnology companies including Infinity Pharmaceuticals Inc. of Cambridge, Massachusetts, and Australia’s ChemGenex Pharmaceuticals Ltd. are working to develop treatments to block the stem cells. Findings released in 2007 showed that one marketed anti-cancer drug, GlaxoSmithKline’s Tykerb, reduced the number of cancer stem cells and helped eliminate the disease in some breast cancer patients.
Tumor-Initiating Cells
Research by Jenny Chang at the Baylor College of Medicine has shown that after breast-cancer patients got chemotherapy or hormone treatments, the remaining malignancy had a greater percentage of tumor-initiating cells than before.
The MIT and Broad researchers grew cancer cells from breast tumors in a way that increased the number of stem cells. They then used rapid screening techniques to test 16,000 commercially available chemical compounds. They identified 32 candidates before settling on salinomycin as the most potent.
They tested the compound in mice in two ways. First, they exposed breast cancer stem cells in laboratory dishes to salinomycin and Taxol and tallied how many cells they would need to inject in a mouse to trigger a tumor. It took many more of the salinomycin-treated cells to spur cancer, showing that the compound was inhibiting cancer development, Gupta said.
Second, they induced tumors in mice and treated them with the two drugs. While both drugs exerted “significant anti-tumor effects,” the mice treated with Taxol had a greater proportion of cancer stem cells left in the remaining tumor. Taxol enriched the population of cancer stem cells and salinomycin reduced it, Gupta said.
“We have now a systematic way to look for compounds that selectively kill cancer stem cells,” Gupta said. “We’ve taken a lot of the serendipity out of the equation.”
The research was funded partly by the National Cancer Institute.
To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.
http://www.bloomberg.com/apps/news?pid=20601124&sid=aQRhuBEamXkU
CBAI up 15% on 100M shares traded. May be a sign that things are starting to happen for the stem cell stocks. - afxm
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This board is created for the discussion of any stem cell stock since the 'stem' sector is heating
up again, finally; for example: astm, stem, gern , ccel.ob, plrs.ob and others feel free to add
& join in the on-topic discussion.
Stocks:
Aastrom (ASTM):
http://finance.yahoo.com/q/ks?s=ASTM
http://finance.yahoo.com/q/pr?s=astm
http://www.investorshub.com/boards/board.asp?board_id=2080
Stem Cells (STEM):
http://finance.yahoo.com/q/ks?s=STEM
http://finance.yahoo.com/q/pr?s=STEM
http://www.investorshub.com/boards/board.asp?board_id=3023
Geron Corporation (GERN)
http://finance.yahoo.com/q/ks?s=gern
http://finance.yahoo.com/q/pr?s=gern
http://www.investorshub.com/boards/board.asp?board_id=1634
Advanced Cell Technology Inc. (ACTC.OB)
http://finance.yahoo.com/q?s=ACTC.OB
http://www.investorshub.com/boards/board.asp?board_id=5319
TISSERA INC (TSSR.OB):
http://finance.yahoo.com/q?s=TSSR.OB
http://finance.yahoo.com/q/h?s=TSSR.OB
Contact:
Tissera, Inc.
(Investor Relations)
Dr. Uri Elmaleh, 972-9-9561151
uri@tissera.com
Source: Tissera, Inc.
BioStem Inc.(BTEM.OB):
http://finance.yahoo.com/q/pr?s=BTEM.OB
http://finance.yahoo.com/q/ks?s=BTEM.OB
http://www.investorshub.com/boards/board.asp?board_id=7996
Stem Cell Innovations:
http://www.investorshub.com/boards/board.asp?board_id=5472
OSIR ~ Osiris Therapeutics (NasdaqGM:OSIR)
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=33470989
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=33471053
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Stem Cell Storage Stocks
Cryo-Cell International Inc. (CCEL.OB)
ccel>>http://finance.yahoo.com/q/ks?s=ccel.ob
http://finance.yahoo.com/q/pr?s=ccel.ob
http://www.investorshub.com/boards/board.asp?board_id=3965
Cord Blood America Inc. (CBAI.OB)
http://www.cordblood-america.com/
http://finance.yahoo.com/q?s=cbai.ob&d=t
http://finance.yahoo.com/q/pr?s=CBAI.OB
http://www.smallcapwatch.com/company.asp?TICKER=cbai
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Thermogenics board: KOOL
http://investorshub.advfn.com/boards/board.aspx?board_id=13388
RESEARCH ARTICLES:
http://news.google.com/news?q=Stem+cell+news&hl=en&um=1&sa=X&oi=news_group&resnum=4&ct=title
http://www.stemcellresearchnews.com/
http://science.bio.org/cloning.news.html
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Charts:
galleryview/stockcharts,http://stockcharts.com/charts/candleglance.php?STEM,KOOL,ASTM,ALNY,CLBE,CBAI,GERN,PSTI|B|L....
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Helpful Links:
http://www.nature.com/stemcells/index.html
http://www.stemcellresearchnews.com/stem_cell_lab__world.htm
http://www.nature.com/stemcells/index.html
http://stemcells.nih.gov/policy/legislation.asp
http://www.stemcellnews.com/
http://www.stemcell.com/
http://www.scirus.com/srsapp/search?
http://www.stemcellresearchnews.com/
Sticky Post: For news in the Stem Cell sector:
http://www.stemcellresearchnews.com/
http://www.stemcellnews.com/
http://www.sciencedaily.com/news/health_medicine/stem_cells/
PL1
http://stemcells.nih.gov/policy/taskForce/workingGroups/resourceaccess/raMembers.asp
http://novocell.com/
Medical World News:
http://investorshub.advfn.com/boards/board.asp?board_id=10777
Thank you for visiting the StemWare board here on IHUB, and please feel free to post information on Stem Cell stocks and Stem Cell news.....PL1
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