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 differentiation of mouse hematopoietic stem cells and progenitors have been investigated. While high concentrations of IL-1 and IL-3 decreased the recovery of primitive cells, maintenance of committed progenitors appeared insensitive to various concentrations of these cytokines. Expansion of multilineage colony-forming bone marrow cells showed a strong concentration dependence on IL-1 and IL-3. When C.B-17 mice were transplanted 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 lethally irradiated recipient mice. In contrast, cells maintained in 200-500 units per ml could only rescue 19% of the mice. Apparently too high concentrations of cytokines may favour the induction of differentiation 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.