Friday, June 02, 2017 10:41:49 AM
"Stem Cells: Balancing the Elite, the Adequate, and the Dysfunctional
Muscle stem cells—also known as satellite cells because they appear to orbit the muscle fiber cells—are activated when muscles are damaged, but not all the stem cells pull their weight.
“We’ve found that the stem cells in our muscle tissue are by molecular identity very similar, but if you ask them to do their job, to replenish muscle tissue, their function is quite varied,” Cosgrove explains. “There are elite performing stem cells, okay stem cells, and really dysfunctional cells. We’ve shown that the balance in these populations becomes altered in the aging process.”
As our tissues age, they accumulate a larger population of dysfunctional cells. By improving the performance of these cells or by shifting the balance so that we have more elite performers as we age, researchers may be able to vastly improve muscle regeneration.
First, they need to be able to differentiate the dysfunctional cells from the elite. With collaborators, Cosgrove has identified key molecular markers for the different classes of performers. “When we profile these stem cells, one cell at a time, we find a lot of unexpected variation in what genes they’re expressing, many of which affect critical regulatory pathways controlling cell fate decisions,” Cosgrove says. “And this variation becomes even more pronounced in muscle tissues from elderly mice and humans and muscular dystrophy samples.”
Studying just how these pathways impact cell fate is a challenge, given the rarity of the cells. Cosgrove is tackling this challenge with new materials and technology.
Engineering Better Stem Cell Microenvironments Outside the Body
It’s an idea many researchers are chasing: plucking healthy muscle stem cells from a biopsy of a patient, reprogramming them outside the body, and transplanting the healthy cells back into the patient. The procedure could provide long-term muscle regeneration by increasing the population of elite cells.
One problem is that stem cells are finicky subjects outside the body. “They need a lot of coaxing, a lot of gentle support and just the right stimulation,” Cosgrove says. Researchers in the field have been able to prompt muscle stem cells to proliferate in culture, but the cells lose their identity and no longer know their role when transplanted back into the body.
“There are a number of environmental variables that stem cells normally interact with—the matrix they adhere to, the nutrients and chemicals they need and don’t want too much of, the three-dimensional architecture of their environment, and so on. All of these variables influence every cell in our body, but they are frequently lost as we take cells out and put them in a tissue culture or petri dish,” Cosgrove says. “What we’re finding, along with many others, is that if we don’t give the cells just the right balance of both mechanical and chemical factors that stimulate their proliferation, they specialize and lose their stem-cell identity.”
TCEL's research involves regrowing the muscle cells themselves, and would be a revolutionary breakthrough.
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