CONCENTRATION-DEPENDENT EFFECTS OF HEMATOPOIETIC GROWTH-FACTORS DURING IN-VITRO EXPANSION OF MOUSE STEM-CELLS AND PROGENITOR CELLS

The effects of cytokine concentrations on proliferation and differenti ation of mouse hematopoietic stem cells and progenitors have been inve stigated, While high concentrations of IL-1 and IL-3 decreased the rec overy of primitive cells, maintenance of committed progenitors appeare d insensitive to various concentrations of these cytokines, Expansion of multilineage colony-forming bone marrow cells showed a strong conce ntration dependence on IL-1 and IL-3. When C.B-17 mice were transplant ed with AA4.1(+) cells from BALB/c fetal liver, cells maintained in 10 -20 units per ml of IL-1, IL-3, and IL-6 were able to rescue 89% of le thally irradiated recipient mice, In contrast, cells maintained in 200 -500 units per ml could only rescue 19% of the mice, Apparently too hi gh concentrations of cytokines may favour the induction of differentia tion of stem cell populations, An alternative explanation could be the presence of accessory cells producing inhibitory factors or cytokines that induce differentiation of stem cells.