TY - JOUR
T1 - 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
AU - De Revel, Thierry
AU - Appelbaum, Frederick R.
AU - Storb, Rainer
AU - Schuening, Friedrich
AU - Nash, Richard
AU - Deeg, Joachim
AU - McNiece, Ian
AU - Andrews, Robert
AU - Graham, Theodore
PY - 1994/6/15
Y1 - 1994/6/15
N2 - 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 μg/kg) for 7 days led to a 5.4- fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 μg/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 μg/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 108 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 108 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-SCF plus low- dose SCF recovered granulocyte function. Recovery to 500 granulocytes/μL 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.
AB - 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 μg/kg) for 7 days led to a 5.4- fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 μg/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 μg/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 108 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 108 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-SCF plus low- dose SCF recovered granulocyte function. Recovery to 500 granulocytes/μL 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.
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U2 - 10.1182/blood.v83.12.3795.bloodjournal83123795
DO - 10.1182/blood.v83.12.3795.bloodjournal83123795
M3 - Article
C2 - 7515722
AN - SCOPUS:0028338452
SN - 0006-4971
VL - 83
SP - 3795
EP - 3799
JO - Blood
JF - Blood
IS - 12
ER -