TRANSPLANTATION Mobilization as a preparative regimen for hematopoietic stem cell transplantation

Current myeloablative conditioning regi-mens for hematopoietic stem cell (HSC) transplantation are associated with sig-nificant morbidity and mortality. Thus, alternative strategies to promote engraft-ment of infused HSCs with increased safety warrant investigation. Using para-biotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 an-tagonist), HSCs exited from marrow, tran-sited 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 4 107 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 engraft-ment further increased (9.1 % 1.7%, P .001). In contrast, in similar experi-ments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These re-sults 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. (Blood. 2006;