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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3764-3771.
Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-09-3593.
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TRANSPLANTATION
Mobilization as a preparative regimen for hematopoietic stem cell transplantation
Jing Chen,
André Larochelle,
Simon Fricker,
Gary Bridger,
Cynthia E. Dunbar, and
Janis L. Abkowitz
From the Medicine/Hematology, University of Washington, Seattle, WA; Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD; and AnorMED, Langley, BC, Canada.
Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3b mice were treated with AMD3100 at 2 hours before the transplantation of 4 x 107 marrow cells, donor cell engraftment was higher (4.6% ± 1.1%) than in control animals (no AMD3100; 1.0% ± 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% ± 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.
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Table 1.. Trafficking of granulocytes, CFU-GMs, and HSCs in marrow of parabiotic mice at baseline and after cytokine or AMD3100 mobilization
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Table 3.. Trafficking of granulocytes, CFU-GMs, and HSCs in spleen, marrow, and blood of parabiotic mice at baseline and after cytokine or AMD3100 mobilization
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