Effects of Interleukins and Hemopoietic Growth Factors on Proliferation of Multipotent Stem Cell and Leukemic Cells.

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Effects of interleukins (IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9) and various hemopoietic growth factors including granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulation factor (GM-CSF), macrophage colony stimulating factor (M-CSF), erythropoietin (Epo), leukemia inhibitory factor (LIF), stem cell factor (SCF), and interferon- (IFN-) on proliferation of multipotential hemopoietic stem cells and leukemic cells were examined using vitro methylcellulose cultures.In murine, our extensive serum-free culture suggests that the existence of primitive hemopoietic progenitors which require both IL-3 and IL-6 for development, and that some primitive hemopoietic progenitors requiring both IL-3 and IL-6 for the substntaial growth may be unable to survive under the condition of IL-3 alone.Murine bone marrow cells cultured with both IL-3 and IL-6 for 6 days in suspension culture were found to exhibit a highly capacity to reconstitute the hemopoietic system of sublethally-irradiated mice than untreated bone marrow cells. The number of colony-forming units in the spleen (CFU-S) increaseased up to 400 times after 5 weeks of culture in the presence of both IL-3 and IL-6. In experiments using human cord blood or bone marrow cells, a synergistic effect of IL-3 and IL-6 on proliferation of hemopoietic progenitors in short-term cultures was observed in some samples. These results the possible clinical application of in vitro stem cell expansion to bone marrow transplantion.We also found that recombinant human IL-6 stimulates murine and human megakaryocyte colonies dose-dependently synergistically with IL-3. IL-6 alone stimulated no only in vivo maturation of megakaryocytes and platelets production in primates treated with IL-6 but also in vitro maturation of human megakaryocytes.