Effects of cytokines on stem cell engraftment depends on time of evaluation post-marrow-infusion

In vitro treatment of bone marrow cells to expand stem cells may lead to impaired hematopoietic long-term reconstitution. Here we report on studies that show that cytokine-treated cells maintain short-term reconstitution, but lose that potential with time posttransplantation. Hematopoietic progenitors assayed in vitro as high- and low-proliferative potential colony-forming cells, when exposed to four cytokines (interleukin (IL)-3, IL-6, IL-11, and stem cell factor) were significantly expanded and induced to enter the cell cycle. A competitive transplant model--which uses BALB/c mice of opposite genders: cytokine-treated male BALB/c marrow cells competed with fresh, noncultured female cells--gave mean engraftment levels of 47 +/- 3% at 1 week posttransplantation, 49 +/- 6% at 3 weeks, 30 +/- 10% at 6 weeks, 26 +/- 9% at 12 weeks, and 15 +/- 3% at 24 weeks. These data were confirmed using a congenic Ly 5.1/5.2 transplant model and suggest either that cytokines act differentially on separate sets of short-term and long-term repopulating cells or act on one population of stem cells to limit long-term repopulation.