title: Myeloid progenitors: a radiation countermeasure that is effective when initiated days after irradiation.
abstract: The aim of this study was to elucidate the potential of mouse myeloid progenitor cells (mMPC) to mitigate lethal doses of (60)Co 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 (60)Co 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 ((60)Co 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 (60)Co 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.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603, USA. vijay.singh@usuhs.edu
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Julie
authors.initials: J
authors.lastname: Christensen
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.forename: Daphne
authors.initials: D
authors.lastname: Gille
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ducey
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.forename: Holger
authors.initials: H
authors.lastname: Karsunky
authors.forename: Anna K
authors.initials: AK
authors.lastname: Sedello
mesh_terms: D054508:Acute Radiation Syndrome / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D015925:Cryopreservation; D016207:Cytokines / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects; D008297:Male; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D011829:Radiation Dosage; D013045:Species Specificity; D016019:Survival Analysis; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects
chemical_list: D016207:Cytokines