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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-08-2663.
Submitted August 30, 2002
Accepted November 1, 2002
Retroviral transduction efficiency of G-CSF+SCF mobilized peripheral blood CD34+ cells is superior to G-CSF or G-CSF+Flt3-L mobilized cells in nonhuman primates
Peiman Hematti, Stephanie E Sellers, Brian A Agricola, Mark E Metzger, Robert E Donahue, and Cynthia E Dunbar*
National Institutes of Health, Hematology Branch, NHLBI, Bethesda, MD, USA
* Corresponding author; email: dunbarc{at}nhlbi.nih.gov.
Gene transfer experiments in nonhuman primates have been shown to be predictive of success in human clinical gene therapy trials. In most nonhuman primate studies, hematopoietic stem cells (HSCs) collected from the peripheral blood or bone marrow after administration of G-CSF+stem cell factor (SCF) have been used as targets, but this cytokine combination is not generally available for clinical use, and the optimum target cell population has not been systematically studied. In our current study we tested the retroviral transduction efficiency of rhesus macaque peripheral blood CD34+ cells collected after administration of different cytokine mobilization regimens, directly comparing G-CSF+SCF versus G-CSF alone or G-CSF+Flt3-L in competitive repopulation assays. Vector supernatant was added daily for 96 hours in the presence of stimulatory cytokines. The transduction efficiency of HSC as assessed by in vitro colony forming assays was equivalent in all five animals tested, but the in vivo levels of mononuclear cell and granulocyte marking was higher at all time points derived from target CD34+ cells collected after G-CSF+SCF mobilization compared to target cells collected after G-CSF (n=3) or G-CSF+Flt3-L (n=2) mobilization. In three of the animals long-term marking levels of 5-25% was achieved, but only originating from the G-CSF+SCF mobilized target cells. Transduction efficiency of HSCs collected by different mobilization regimens can vary significantly, and is superior with G-CSF+SCF administration. The difference in transduction efficiency of HSCs collected from different sources should be considered whenever planning clinical gene therapy trials and preferably be tested directly in comparative studies.
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