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

In vitro treatment of bone marrow cells to expand stem cells may lead to im paired hematopoietic long-term reconstitution. Here we report on studies th at show that cytokine-treated cells maintain short-term reconstitution, but lose that potential with time posttransplantation. Hematopoietic progenito rs assayed in vitro as high- and low-proliferative potential colony-forming cells. when exposed to four cytokines (interleukin (IL)-3, IL-6, IL-11, an d stem cell factor) were significantly expanded and induced to enter the ce ll cycle. A competitive transplant model--which uses BALB/c mice of opposit e genders: cytokine-treated male BALB/c marrow cells competed with fresh. n oncultured female cells--gave mean engraftment levels of 47 +/- 3% at 1 wee k 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 ac t differentially on separate sets of short-term and long-term repopulating cells or act on one population of stem cells to limit long-term repopulatio n. (C) 1999 The Japanese Society of Hematology.