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4 May 2012 Myeloid Progenitors: A Radiation Countermeasure that is Effective when Initiated Days after Irradiation
Vijay K Singh, Julie Christensen, Oluseyi O Fatanmi, Daphne Gille, Elizabeth J Ducey, Stephen Y Wise, Holger Karsunky, Anna K Sedello
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Abstract

The aim of this study was to elucidate the potential of mouse myeloid progenitor cells (mMPC) to mitigate lethal doses of 60Co γ radiation and X rays in various strains of mice. Different cell doses of pooled allogeneic mMPC generated ex vivo from AKR, C57Bl/6, and FVB mice were transfused intravenously into haplotype-mismatched recipient Balb/c or CD2F1 mice at various times after irradiation to assess their effect on 30-day survival. Our results show that cryopreserved allogeneic mMPC significantly improve survival in both strains of mice irradiated with lethal doses of 60Co γ radiation (CD2F1, 9.2 Gy) and X-ray exposures (Balb/c, 9 Gy) that are known to cause acute radiation syndrome in hematopoietic tissues. Survival benefit was mMPC-dose dependent and significant even when mMPC administration was delayed up to 7 days after irradiation. We further show that mMPC administration mitigates death from acute radiation syndrome at radiation doses of up to 15 Gy (60Co γ radiation, CD2F1), which are radiation exposure levels that cause mice to succumb to multi-organ failure, and determined that the dose-reduction factor of 5 million mMPC administered 24 h after irradiation of CD2F1 mice is 1.73. Even at high doses of up to 14 Gy 60Co γ radiation, mMPC administration could be delayed up to 5 days in CD2F1 mice and still provide significant benefit to 30-day survival. These results demonstrate that mMPC are a promising radiation countermeasure with the potential to mitigate radiation injury in unmatched recipients across a broad range of lethal radiation doses, even when administration is delayed days after radiation exposure. With respect to efficacy, timing, and practicality of administration, mMPC appear to be a very promising radiation countermeasure for acute radiation syndrome among all candidate therapeutics currently under development.

Vijay K Singh, Julie Christensen, Oluseyi O Fatanmi, Daphne Gille, Elizabeth J Ducey, Stephen Y Wise, Holger Karsunky, and Anna K Sedello "Myeloid Progenitors: A Radiation Countermeasure that is Effective when Initiated Days after Irradiation," Radiation Research 177(6), 781-791, (4 May 2012). https://doi.org/10.1667/RR2894.1
Received: 8 December 2011; Accepted: 1 February 2012; Published: 4 May 2012
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