Synergistic effect of stem cell factor with interleukin-3 or granulocyte-macrophage colony-stimulating factor on the proliferation of murine primitive hematopoietic progenitors.

We examined the effect of recombinant murine stem cell factor (SCF) on murine primitive hematopoietic stem cells in vivo. Marrow cells from 5-fluorouracil (5-FU)-treated male CBA/J mice were transplanted into lethally irradiated female littermates. Immediately after marrow transplant, the mice received SCF, interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination daily for 6 days. Day-12 colony-forming units-spleen (CFU-S) and marrow-derived colony-forming units-granulocyte/macrophage (CFU-GM) were assessed. Bone marrow cells from primary transplant recipients were transplanted into a secondary group of lethally irradiated mice, and the number of spleen colonies arising after 12 days' engraftment was determined as pre-CFU-S. SCF alone did not increase spleen colony formation in either primary or secondary recipients. In contrast, treatment of primary recipients with SCF and GM-CSF or IL-3 or with all three cytokines resulted in a synergistic increase of CFU-S in secondary recipients, indicating increased pre-CFU-S levels. The cytokine combinations also produced synergistic increases of CFU-GM in primary recipient marrow. Evaluation of spleen colonies in secondary recipients by PCR amplification of the Y-chromosome sex-determining region indicated that about 80% were of donor (male) origin. We conclude that SCF with IL-3 and/or GM-CSF increases pre-CFU-S proliferation.