Abstract

Recombinant stem cell factor (SCF) is the ligand for c-kit, a cell surface receptor with tyrosine kinase activity. In vitro, SCF alone stimulates little proliferation of bone marrow hematopoietic colony-forming cells (CFC). However, SCF enhances both the number and size of colonies formed in response to various cytokines. Importantly, SCF also enhances the in vitro generation of CFC from purified bone marrow precursor populations studied at a clonal level. In vivo administration of human SCF to normal baboons enhances the number of circulating granulocyte-macrophage colony-forming units (CFU-gm) and erythroid burst-forming units (BFU-e) 10- to 100-fold. CFU-mix and high proliferative potential (HPP)-CFC do not normally circulate, but after SCF treatment, seven out of seven baboons had detectable circulating levels of these progenitors.

We have examined the effects of rat SCF on hematopoietic recovery after otherwise lethal total body irradiation. The LD50 for the control BDF1 mice used in these studies is between 1000–1050 cGy and 1250–1350 cGy for mice receiving only three injections of rat SCF. The most significant contribution to the radioprotective effect is due to pretreatment with rat SCF. We examined the recovery of bone marrow progenitors and mature peripheral blood cells relative to irradiated control mice. The rate of recovery of bone marrow progenitors in the SCF-treated mice was faster than in the controls, with a small difference in the total WBC between the two groups during the time (10 days post irradiation) when 90% of control mice and 0% of the SCF-treated mice were dead. There was a significant difference in platelet counts and neutrophils in the marrow between controls and SCF-treated mice which may have contributed to the death of control mice. Additional effects on other organ systems are being examined.

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