Abstract
Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×106 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective “off the shelf” therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia.
Highlights
Radiation accidents such as those in Fukushima (2010), Goiania, Brazil (1988), in Tokai-Mura, Japan (1999) and in higher scale in Chernobyl (1986) [1,2,3,4] serve as a warning sign of the hazards associated with potential future catastrophic nuclear events
Matched hematopoietic stem cells (HSC) transplantation may be a remedy of choice for the salvation of the eradicated bone marrow (BM), but it is not practical as an immediate treatment in an event associated with high dose exposure of many individuals
Other treatments could be based on growth factors, mainly granulocyte and granulocytemacrophage colony stimulating factors (G-CSF and GM-CSF), which were approved as supportive treatment for BM regeneration following radiotherapy or chemotherapy and for enhancement of the engraftment of HSC in BM transplantation
Summary
Radiation accidents such as those in Fukushima (2010), Goiania, Brazil (1988), in Tokai-Mura, Japan (1999) and in higher scale in Chernobyl (1986) [1,2,3,4] serve as a warning sign of the hazards associated with potential future catastrophic nuclear events. The use of radical scavenger and DNA protecting agent WR2721 (Amifostine or Ethyol) [21], given before or very short time after radiation exposure was recently approved for the alleviation of clinical radiation symptoms [22,23,24,25,26]. Still none of those treatments could be considered as an ultimate life saving drug in cases of lethal high dose irradiation
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