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

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1975-1980 ◽  
Author(s):  
RG Andrews ◽  
GH Knitter ◽  
SH Bartelmez ◽  
KE Langley ◽  
D Farrar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Absolute Number ◽  
Human Stem Cell ◽  
Clinical Role ◽  
Gm Csf ◽  
Macrophage Colony ◽  
Human Stem Cell Factor

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.

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

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1975-1980 ◽  
Author(s):  
RG Andrews ◽  
GH Knitter ◽  
SH Bartelmez ◽  
KE Langley ◽  
D Farrar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Absolute Number ◽  
Human Stem Cell ◽  
Clinical Role ◽  
Gm Csf ◽  
Macrophage Colony ◽  
Human Stem Cell Factor

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.

scholarly journals Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3203-3211 ◽  
Author(s):  
MK Majumdar ◽  
ET Everett ◽  
X Xiao ◽  
R Cooper ◽  
K Langley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transgenic Mice ◽  
Stem Cell Factor ◽  
Coat Color ◽  
Protein Product ◽  
Cell Surface Expression ◽  
Human Stem Cell ◽  
Human Stem Cell Factor

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220- expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.

Membrane-Bound Human Stem Cell Factor Promotes Differentiation of Human Granulocytes and Mast Cells In Vivo,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3419-3419
Author(s):  
Shinsuke Takagi ◽  
Yoriko Saito ◽  
Atsushi Hijikata ◽  
Satoshi Tanaka ◽  
Takashi Watanabe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Myeloid Cells ◽  
Human Stem Cell ◽  
Myeloid Development ◽  
Membrane Bound ◽  
Human Stem Cell Factor

Abstract Abstract 3419 Recently, advances in xenograft models for human hemamtopoietic stem cells (HSCs), or the humanized mice, have begun to allow investigators to examine the differentiation of human hematopoietic and immune cells in vivo. However, lymphoid-skewed human hematopoietic development in the mouse bone marrow is one of the remaining limitations in the humanized mouse models. The inefficient human myeloid development could at least partly be attributed to the mouse microenvironment not fully supporting differentiation and maturation of human myeloid lineage. To overcome this problem, we focused on the role of membrane-bound human stem cell factor in supporting the maintenance of human HSCs and inducing the development of human myeloid cells and created human stem cell factor transgenic NOD/SCID/IL2rgKO (hSCF Tg NSG) mice. Transplantation of 5000–50000 cord blood-derived Lin-CD34+CD38- cells resulted in significantly higher engraftment of human CD45+ leukocytes at 3–6 months post-transplantation in the bone marrow, spleen, and peripheral blood of hSCF Tg NSG recipients compared with those of non-transgenic NSG recipients. The enhanced human CD45+ engraftment was most prominent in the bone marrow (hSCF Tg recipients: 98.0 +/− 1.3%, n= 15, non-Tg NSG controls: 75.3 +/− 7.3%, n=7). In the bone marrow, the frequency of human CD33+ myeloid cells within the total human CD45+ population was significantly higher in the hSCF Tg NSG recipients than in the non-Tg NSG recipients and constituted the majority of human hematopoietic cells (hSCF Tg recipients: 54.6 +/− 4.5%, n=15 and non-Tg NSG controls: 29.3 +/− 4.0%, n=7). Flow cytometric analysis demonstrated that the majority of engrafted human myeloid cells in the hSCF Tg recipient bone marrow were side-scatter high, HLA-DR negative granulocytes. Reflecting the effect of human SCF on the development of human mast cells, human c-Kit+CD203c+ mast cells were identified in the bone marrow, spleen, and gastrointestinal tracts of the hSCF Tg NSG recipients. Altogether, the in vivo humanized mouse model demonstrates the essential role of membrane-bound SCF in human myeloid development. The hSCF Tg NSG humanized mice may facilitate the in vivo investigation of human HSCs, myeloid progenitors and mature myeloid lineage. Disclosures: No relevant conflicts of interest to declare.

Effects of recombinant human stem cell factor (SCF) on the growth of human progenitor cells in vitro

1991 ◽  
Vol 148 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Giovanni Migliaccio ◽  
Anna Rita Migliaccio ◽  
Maurice L. Druzin ◽  
Patricia-Jane V. Giardina ◽  
Krisztina M. Zsebo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Human Stem Cell ◽  
Human Stem Cell Factor

Human stem cell factor does not affect the morphology and expression of functionally relevant molecules of Langerhans cells in vitro

1998 ◽  
Vol 16 ◽  
pp. S96
Author(s):  
Francesca Prignano ◽  
Gianni Gerlini ◽  
Nicola Pimpinelli ◽  
Paolo Romagnoli ◽  
Benvenuto Giannotti
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Langerhans Cells ◽  
Human Stem Cell ◽  
Human Stem Cell Factor

scholarly journals In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons enhanced circulation of progenitor cells

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 800-810 ◽  
Author(s):  
RG Andrews ◽  
RA Briddell ◽  
GH Knitter ◽  
T Opie ◽  
M Bronsden ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Low Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Human Stem Cell ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Human Stem Cell Factor

Abstract Recombinant human stem cell factor (rhSCF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) are synergistic in vitro in stimulating the proliferation of hematopoietic progenitor cells and their precursors. We examined the in vivo synergy of rhSCF with rhG-CSF for stimulating hematopoiesis in vivo in baboons. Administration of low-dose (LD) rhSCF (25 micrograms/kg) alone did not stimulate changes in circulating WBCs. In comparison, administration of LD rhSCF in combination with rhG-CSF at 10 micrograms/kg or 100 micrograms/kg stimulated increases in circulating WBCs of multiple types up to twofold higher than was stimulated by administration of the same dose of rhG-CSF alone. When the dose of rhG-CSF is increased to 250 micrograms/kg, the administration of LD rhSCF does not further increase the circulating WBC counts. Administration of LD rhSCF in combination with rhG-CSF also stimulated increased circulation of hematopoietic progenitors. LD rhSCF alone stimulated less of an increase in circulating progenitors, per milliliter of blood, than did administration of rhG-CSF alone at 100 micrograms/kg. Baboons administered LD rhSCF together with rhG-CSF at 10, 100, or 250 micrograms/kg had 3.5- to 16-fold higher numbers per milliliter of blood of progenitors cells of multiple types, including colony-forming units granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming and burst-forming units-megakaryocyte (CFU- MK and BFU-MK) compared with animals given the same dose of rhG-CSF without rhSCF, regardless of the rhG-CSF dose. The increased circulation of progenitor cells stimulated by the combination of rhSCF plus rhG-CSF was not necessarily directly related to the increase in WBCs, as this effect on peripheral blood progenitors was observed even at an rhG-CSF dose of 250 micrograms/kg, where coadministration of LD rhSCF did not further increase WBC counts. Administration of very-low- dose rhSCF (2.5 micrograms/kg) with rhG-CSF, 10 micrograms/kg, did not stimulate increases in circulating WBCs, but did increase the number of megakaryocyte progenitor cells in blood compared with rhG-CSF alone. LD rhSCF administered alone for 7 days before rhG-CSF did not result in increased levels of circulating WBCs or progenitors compared with rhG- CSF alone. Thus, the synergistic effects of rhSCF with rhG-CSF were both dose- and time-dependent. The doses of rhSCF used in these studies have been tolerated in vivo in humans.(ABSTRACT TRUNCATED AT 400 WORDS).

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