Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs.
The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long-term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.
de Revel
T
T
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092.
Appelbaum
F R
FR
Storb
R
R
Schuening
F
F
Nash
R
R
Deeg
J
J
McNiece
I
I
Andrews
R
R
Graham
T
T
D000818:Animals; D016026:Bone Marrow Transplantation; D004285:Dogs; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007937:Leukapheresis; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor