Myeloid progenitors: a radiation countermeasure that is effective when initiated days after irradiation

Radiat Res. 2012 Jun;177(6):781-91. doi: 10.1667/rr2894.1. Epub 2012 May 4.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Radiation Syndrome / metabolism
  • Acute Radiation Syndrome / pathology
  • Acute Radiation Syndrome / therapy*
  • Animals
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Cryopreservation
  • Cytokines / metabolism
  • Gamma Rays / adverse effects
  • Male
  • Mice
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / metabolism*
  • Radiation Dosage
  • Species Specificity
  • Survival Analysis
  • Time Factors
  • X-Rays / adverse effects

Substances

  • Cytokines