The effect of multidrug-resistance 1 gene versus neotransduction on ex vivo and in vivo expansion of rhesus macaque hematopoietic repopulating cells

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Abstract
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 ofMDR1-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 eitherMDR1 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 bothMDR 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 neovector–containing cells. There was no evidence for expansion ofMDR1 vector–transduced cells. Long-term engraftment with MDR1 vector– and neo vector–transduced cells occurred despite prolonged culture.

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