Pluristem Therapeutics Inc (PSTI)

[FDApproved]

Pre-Administration of PLX-R18 Cells Protects Mice from Radiation-Induced Hematopoietic Failure and Lethality


Flt3L has been reported as an efficacy biomarker of bone marrow damage and SAA and PCT was reported as marker of sepsis following organ damage [37,38]. All these protein levels are significantly increased after radiation with time as expected, however, PLX-R18 pre-treatment lowered these protein levels and brought them back to near basal levels. [b[color=red]]This suggests that part of the radioprotection afforded by PLX-R18 is the result of reducing bone marrow damage and sepsis following radiation exposure in mice.[/color]

The protection afforded by PLX-R18 to the hematopoietic system after irradiation was evidenced by the accelerated recovery of white blood cell, lymphocyte, neutrophil, and platelet counts (most notably on Day 21 after irradiation), compared to vehicle-treated animals as observed previously by us with other promising countermeasures [32,33,43]. Although PLX-R18 treatment was unable to restore sternal megakaryocyte counts and clonogenic potential of femoral bone marrow cells to the levels observed in non-irradiated animals, both parameters were significantly higher by Day 30 after irradiation in PLX-R18-treated animals than in PlasmaLyte-treated counterparts, demonstrating the ability of PLX-R18 to aid in the recovery of femoral and sternal bone marrow stem cells. Furthermore, femoral bone marrow clonogenic potential assessed on Day 45 in the PLX-R18-treated group demonstrated continued improvement of this parameter.

Conclusions

In conclusion[color=red][/color], our data show the systemic effect of PLX-R18 pre-treatment protects mice from radiation-induced bone marrow aplasia and rescues them from lethality. In addition to attenuating hematopoietic and immune system dysfunction, PLX-R18 also reduces vascular oxidative stress and pro-inflammatory cytokines/chemokines and growth factors, inhibited the expression of pAKT. Further studies need to be conducted to explore the detailed mechanism and cascade of events contributing to the radioprotection afforded by PLX-R18 cells. Evaluating the efficacy of this countermeasure on female mice would also add value to the studies that could be included for an FDA IND application. Further development of PLX-R18 as a radioprotectant could have a significant impact on radiation biology, radiation oncology, and military medicine.

https://www.mdpi.com/2073-4425/13/10/1756/htm