The effects of SCF/G-CSF prestimulation on radiation sensitivity and engraftment in nonmyeloablated murine hosts

Objective. Previous studies have shown improved engraftment in a murine mod el when granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) were administered for 5 days prior to irradiation, with significant l evels of engraftment in the growth factor-preconditioned group even at very low radiation doses. We sought to explore the mechanisms behind this effec t, Methods. The radiation sensitivity of mice with or without 5 days of presti mulation with G-CSF (200 mug/kg/d) and SCF (50 mug/kg/d) was compared. To f urther evaluate whether growth factor prestimulation enhances engraftment b y mobilization of hematopoietic progenitors into peripheral blood, thus cre ating less endogenous competition within the marrow compartment, female mic e were pretreated with 5 days of G-CSF/SCF or control diluent, Engraftment of 40 X 10(6) peripheral blood stem cells (PBSCs) harvested from G-CSF/SCF- mobilized male mice was compared in the two recipient groups. Results, There was no difference in survival between the pretreated and con trol mice at the radiation doses tested. Additionally, there was no signifi cant difference in the recovery of blood counts, bone marrow cellularity, c olony-forming unit (CFU) content, or stem cell numbers assessed 4 months la ter in a competitive repopulation model. Engraftment levels of male cells d id not differ between G-CSF/SCF-pretreated and control recipients, and coul d be detected in 30% of recipients at 20-24 weeks (4/12 in each group) at o verall levels of 0.1-1%, Conclusions. The enhanced engraftment in cytokine pretreated recipients is unlikely to be due to increased endogenous stem-cell killing or to the crea tion of endogenous marrow "space" by egress of endogenous stem cells after cytokine prestimulation. (C) 2001 International Society for Experimental He matology. Published by Elsevier Science Inc.