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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3772-3778.
Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-09-3592.
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Submitted September 6, 2005
Accepted December 19, 2005
AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in non-human primates
Andre Larochelle, Allen Krouse, Mark Metzger, Donald Orlic, Robert E Donahue, Simon Fricker, Gary Bridger, Cynthia E Dunbar*, and Peiman Hematti
National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
AnorMED Inc., Langley, BC, Canada
* Corresponding author; email: dunbarc{at}nhlbi.nih.gov.
AMD3100, a bicyclam antagonist of the chemokine receptor CXCR4, has been shown to induce rapid mobilization of CD34+ hematopoietic cells in mice, dogs, and humans, offering an alternative to G-CSF mobilization of peripheral blood hematopoietic stem cells. In this study, AMD3100-mobilized CD34+ cells were phenotypically analyzed, marked with neoR-containing retroviral vectors and subsequently transplanted in myeloablated rhesus macaques. We show engraftment of transduced AMD3100-mobilized CD34+ cells with neoR gene marked myeloid and lymphoid cells up to 32 months after transplantation, demonstrating the ability of AMD3100 to mobilize true long-term repopulating hematopoietic stem cells. More AMD3100-mobilized CD34+ cells are in the G1 phase of the cell cycle and more cells express CXCR4 and VLA-4 compared to G-CSF-mobilized CD34+ cells. In vivo gene marking levels obtained with AMD3100-mobilized CD34+ cells were better than those obtained using CD34+ cells mobilized with G-CSF alone. Overall, these results indicate that AMD3100 mobilizes a population of hematopoietic stem cells with intrinsic characteristics different from those of hematopoietic stem cells mobilized with G-CSF, suggesting fundamental differences in the mechanism of AMD3100-mediated and G-CSF-mediated hematopoietic stem cell mobilization. Thus, AMD3100-mobilized CD34+ cells represent an alternative source of hematopoietic stem cells for clinical stem cell transplantation and genetic manipulation with integrating retroviral vectors.

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