The effect of multidrug-resistance 1 gene versus neo transduction on ex vivo and in vivo expansion of rhesus macaque hematopoietic repopulating cells.
Transduction of murine stem cells with a multidrug-resistance 1 gene (MDR1) retrovirus results in dramatic ex vivo and in vivo expansion of repopulating cells accompanied by a myeloproliferative disorder. Given the use of MDR1-containing vectors in human trials, investigations have been extended to nonhuman primates. Peripheral blood stem cells from 2 rhesus monkeys were collected, CD34-enriched, split into 2 portions, and transduced with either MDR1 vectors or neo vectors and continued in culture for a total of 10 days before reinfusion. At engraftment, the copy number in granulocytes was extremely high from both MDR vectors and neo vectors, but the copy number fell to 0.01 to 0.05 for both. There were no perturbations of the leukocyte count or differential noted. After 3 cycles of stem cell factor/granulocyte colony-stimulating factor, there were no changes in the levels of MDR1 vector- or neo vector-containing cells. There was no evidence for expansion of MDR1 vector-transduced cells. Long-term engraftment with MDR1 vector- and neo vector-transduced cells occurred despite prolonged culture.
Hematology Branch, the National Heart, Lung, and Blood Institute, and the Molecular and Clinical Hematology Branch, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD 20892, USA.
S E
SE
Sellers
J F
JF
Tisdale
B A
BA
Agricola
M E
ME
Metzger
R E
RE
Donahue
C E
CE
Dunbar
B P
BP
Sorrentino
D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018628:Gene Dosage; D019450:Genes, MDR / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods* / Q000592:standards; D005822:Genetic Vectors / Q000009:adverse effects / Q000592:standards; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D023421:Models, Animal; D009355:Neomycin; D014161:Transduction, Genetic / Q000379:methods / Q000592:standards
D009355:Neomycin