Enhancement of mixed hematopoietic chimerism by CXCR4 blockade in mice receiving allogeneic bone marrow transplantation without irradiation

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	IMMUNO/INFLAM-14

* FARE Award Winner

Authors

• ZZ Li
• X Xu
• I Weiss
• O Jacobson
• E Schneider
• JL Gao
• D McDermott
• J Farber
• P Murphy

Abstract

Solid organ allograft tolerance can be achieved by establishing mixed hematopoietic chimerism in recipients through transplantation of bone marrow (BM) from donors. Currently, clinical application is limited by requirements for mega-doses of BM cells and irradiation. AMD3100 is an FDA-approved CXCR4 antagonist that rapidly and transiently mobilizes hematopoietic cells from BM niches to blood. We hypothesized that AMD3100 may enhance mixed chimerism with less conditioning by providing a competitive advantage to reoccupy BM niches for infused donor BM cells over released recipient BM cells. We tested this in a preclinical transplantation protocol in mice. All mice received transient CD40L blockade, CD8 depletion and rapamycin, without irradiation. Mice receiving 50 million allogeneic donor BM cells attained 1.28% chimerism 1 month post-transplant, whereas mice receiving 10-25 million donor cells attained < 0.87% chimerism. Mice injected with 10 mg/kg AMD3100 at 1 hour, or at 10 hrs, or at both 1 hour and 10 hours before receiving 20 million allogeneic BM cells attained 1.52%, 0.56% and 1.49% chimerism, respectively; the middle value is similar to saline controls. In mice, ~1% chimerism is the threshold required for donor-specific tolerance. We conclude that AMD3100 may enhance mixed chimerism in non-irradiated mice receiving allogeneic BM transplants.

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