A c-kit ligand, recombinant human stem cell factor, mediates reversible expansion of multiple CD34+ colony-forming cell types in blood and marrow of baboons.
The ligand for the human c-kit, recombinant human stem cell factor (SCF), was administered to baboons at doses of 200, 100, 50, 25, and 10 micrograms/kg/d. SCF induced a dose-dependent expansion of hematopoietic colony-forming cells (CFC) of multiple types in both blood and marrow, including colony-forming unit (CFU) granulocyte-monocyte, burst-forming unit-erythroid, CFU-MIX, and high proliferative potential-CFC. These changes were associated with a dose-dependent leukocytosis, involving all leukocyte lineages, a reticulocytosis, and increases in marrow cellularity. At 200 micrograms/kg/d of SCF, CFC in blood were increased 10-fold to greater than 100-fold. This correlated with an increased frequency of CD34+ cells in blood. The frequency of CFC in blood approached that of marrow in some animals. These changes were reversed within 7 to 14 days of stopping SCF. The results of these studies suggest a role for the c-kit ligand in stimulating the expansion of multiple CFC types in blood and marrow for potential therapeutic purposes.
Andrews
R G
RG
Pediatric Oncology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Bartelmez
S H
SH
Knitter
G H
GH
Myerson
D
D
Bernstein
I D
ID
Appelbaum
F R
FR
Zsebo
K M
KM
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D010215:Papio; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D019089:Stem Cell Factor