Stem cell factor and basic fibroblast growth factor are synergistic in augmenting committed myeloid progenitor cell growth.
Stem cell factor (SCF) and basic fibroblast growth factor (bFGF) are hematopoietic cytokines produced by bone marrow stromal cells. It is known that, although SCF and bFGF have limited clonogenic activity on their own, they can augment colony-stimulating factor (CSF)-mediated progenitor cell growth. Because these factors are both sequestered by stromal cells, we examined their interaction on progenitor cell growth in conjunction with granulocyte-macrophage-CSF (GM-CSF). In this study, we show that clonogenic growth derived from low-density bone marrow cells stimulated by GM-CSF is significantly augmented (P < .001) in the presence of maximal (100 ng/mL) concentrations of SCF in combination with 100 ng/mL of bFGF. When CD34+ cells are used, the synergistic effect of bFGF and SCF for GM-CSF-mediated progenitor cell growth is further increased, resulting in as much as a sevenfold increase in detectable colony-forming units granulocyte-macrophage (P < .001). These data suggest that the synergistic activity of bFGF and SCF is mediated directly on hematopoietic precursors. These observations suggest that bFGF and SCF, concentrated locally on stromal cell surfaces, might interact in concert with other hematopoietic cytokines to regulate stem cell proliferation and differentiation in hematopoietic niches in the bone marrow.
Gabrilove
J L
JL
Laboratory of Leukocyte Biology, Sloan Kettering Institute, New York, NY 10021.
White
K
K
Rahman
Z
Z
Wilson
E L
EL
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor