Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates

Abstract

Recombinant human stem cell factor (SCF) is homologous with recombinant rat SCF (rrSCF) and is a ligand for c-kit. We determined the influence of SCF on hematopoiesis in vitro and in vivo in baboons. In vitro, SCF alone stimulated little growth of hematopoietic colony-forming cells from baboon marrow, but did increase the number of colonies formed in response to erythropoietin (Epo), interleukin-3 (IL-3), and granulocyte- macrophage colony-stimulating factor (GM-CSF). In vivo, SCF caused an increase in the peripheral blood of the number of erythrocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In marrow, it caused an increase in marrow cellularity and in the absolute number of colony-forming unit-granulocyte-monocyte (CFU-GM) and burst- forming unit-erythroid (BFU-E) in marrow following infusion of SCF. The in vivo stimulation of multiple lymphohematopoietic lineages corroborates previous in vitro studies and suggests a potentially important clinical role for SCF.

Paradoxical drop in circulating neutrophil count following granulocyte-colony stimulating factor and stem cell factor administration in rhesus macaques

“…This hematopoietic growth factor has become the standard of care for the treatment of patients with genetic and chemotherapy-related neutropenia [4][5][6]8,14,15], and is regularly used to mobilize hematopoietic stem and progenitor cells into circulation so that they can easily be collected by leukapheresis for transplantation [7,16,17]. SCF has been molecularly cloned [18][19][20] and synergistically augments mobilization when given in combination with G-CSF [7,16,17,21]. The combination of G-CSF and SCF is regularly used in non-human primates (NHPs) to maximize the number of CD34 + hematopoietic stem cells in circulation [22].…”

Spontaneous dissociation-association of monomers of the human-stem-cell-factor dimer

“…On haematopoietic progenitors in vitro, SCF is synergistic with other cytokines and colony-stimulating factors (CSFs) in promoting colony formation [1,2,[11][12][13][14][15][16]. In vivo, exogenously provided SCF can increase the levels of progenitors and mature cells of multiple haematopoietic lineages in the bone marrow and peripheral blood [3,17,18]. The mobilization of progenitors to the peripheral blood is striking, and the effects of SCF are synergistic with those of granulocyte CSF [19,20].…”