Stem Cell Factor Gene Research Articles

The Role of Cytokines in Human Endometrium: The Inhibitory Effect of IL-1 and TNF α on <I>in Vitro</I> Decidualization and mRNA Expression of M-CSF, SCF and LIF in the Human Endometrium

With a culture system of human endometrial stromal cells, the effects of cytokines of interleukin (IL)-1, tumor necrosis factor (TNF)α, interferon (IFN)β, and IFNγ were examined. In a dose-dependent manner, IL-1 and TNFα inhibited progesterone-induced in vitro decidualization indicated by PRL production and cellular transformation with no cytotoxicity. IFNβ had no effect, but IFNγ inhibited PRL production caused by cytotoxicity. By Northern blot analysis and quantitative reverse transcription-polymerase chain reaction, human endometrium was shown to express the genes of macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF) and leukemia inhibitory factor (LIF). During stromal cell culture with progesterone, mRNA expression of both M-CSF and its receptor, c-fms, was significantly increased in a dose- and time-dependent manner. There was no difference in the expression of SCF mRNA between proliferative and secretory phase endometrium, but higher expression of SCF mRNA was observed in decidua of early pregnancy. LIF mRNA was more strongly expressed in secretory phase endometria than in proliferative ones. In culture experiments, SCF gene expression was higher in stromal cells, on the other hand, LIF mRNA was more strongly expressed in glandular epithelial cells. But no significant changes in SCF or LIF mRNAs were identified in our culture system for in vitro decidualization. These findings suggested an important regulatory role of cytokines in endometrial differentiation, and, in addition, endometrial stromal cells and glandular cells may play independent roles in producing cytokines essential for local immune cell proliferation and/or differentiation. Thus an immune-endocrine network exists in the human uterus to regulate the endometrial function.

The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor

Stem cell factor (SCF) is the ligand for the receptor encoded by the c- kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.

The Effects on Hematopoiesis of Recombinant Stem Cell Factor (Ligand for c-kit) Administered In Vivo to Mice Either Alone or in Combination With Granulocyte Colony-Stimulating Factor

Stem cell factor (SCF) is the ligand for the receptor encoded by the c-kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.

Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium

We have Identified a novel growth factor, stem cell factor (SCF), for primitive hematopoietic progenitors based on its activity on bone marrow cells derived from mice treated with 5-fluorouracil. The protein was isolated from the medium conditioned by Buffalo rat liver cells. It is heavily glycosylated, with both N-linked and O-linked carbohydrate. Amino acid sequence following removal of N-terminal pyroglutamate is presented. The protein has potent synergistic activities in semisolid bone marrow cultures in conjunction with colony-stimulating factors. It is also a growth factor for mast cells. In two companion papers, we present the sequences of partial SCF cDNAs, identify SCF as a c- kit ligand, and map the SCF gene to the SI locus of the mouse.