EFFECT OF RECOMBINANT STEM-CELL FACTOR ON CLONOGENIC MATURATION AND CYCLE STATUS OF HUMAN FETAL HEMATOPOIETIC PROGENITORS

Studies were undertaken to delineate the actions of stem cell factor ( SCF) on human fetal hematopoietic progenitors in vitro. Mononuclear ce lls from umbilical cord blood of term fetuses were ''panned'' immunolo gically, and the resulting hematopoietic progenitors were grown in met hylcellulose culture containing various concentrations of SCF alone or in combination with other recombinant hematopoietic growth factors. N eutralizing antibodies to IL-3 and granulocyte-macrophage colony-stimu lating factor were added to all plates to which recombinant IL-3 or gr anulocyte-macrophage colony-stimulating factor were not included to de crease any confounding effect resulting from production of small quant ities of these factors within the culture plates. SCF, as a single age nt, supported clonogenic maturation of fetal granulocyte-macrophage pr ogenitors (granulocyte-macrophage colony-forming unit, p < 0.05), mult ipotent progenitors (CFU-MIX, p < 0.05), and erythroid progenitors (er ythroid burst-forming unit, p < 0.05). When combined with subplateau c oncentrations (0.1 mu g/L) of IL-3 or granulocyte-macrophage colony-st imulating factor, SCF had an additive or synergistic effect on clonoge nic maturation of granulocyte-macrophage colony-forming unit and CFU-M IX. When combined with higher concentrations (5.0 mu g/L) of IL-3 or g ranulocyte-macrophage colony-stimulating factor, SCF generally did not enhance colony formation but did increase the number of cells per col ony. Like other pleiotropic cytokines such as IL-6, IL-9, and IL-11, S CF had a broad spectrum of action of fetal hematopoietic progenitors.