Rapid Engraftment by Peripheral Blood Progenitor Cells Mobilized by Recombinant Human Stem Cell Factor and Recombinant Human Granulocyte Colony-Stimulating Factor in Nonhuman Primates

• Published in: Blood 1995-01, Vol.85 (1), p.15-20
• Main Authors: Andrews, Robert G., Briddell, Robert A., Knitter, Glenn H., Rowley, Scott D., Appelbaum, Frederick R., McNiece, Ian K.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood Cell Count; Bone marrow, stem cells transplantation. Graft versus host reaction; Graft Survival; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Cell Growth Factors - administration & dosage; Hematopoietic Cell Growth Factors - pharmacology; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Leukapheresis; Leukocyte Count; Medical sciences; Neutrophils - cytology; Papio; Platelet Count; Recombinant Proteins - pharmacology; Stem Cell Factor; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V85.1.15.bloodjournal85115

We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 μg/kg/d) plus rhG-CSF (100 μg/ kg/d) while a second group received rhG-CSF alone (100 μg/ kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopre-served autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of >20,000 was 8 days ± 0, to a white blood cell count (WBC) of >1,000 was 11 ± 1 days, and to an absolute neutrophil count (ANC) of >500 was 12 ± 1 days. These results compared with 42 ± 12, 16 ± 1, and 24 ± 4 days to achieve platelets >20,000, WBC >1,000, and ANC >500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG-CSF alone.