Plastic Surgery Research Council
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INFUSED BONE MARROW FAILS TO PROLONG VASCULARIZED COMPOSITE ALLOGRAFT SURVIVAL IN NONHUMAN PRIMATES
Presenter: Philip Brazio, BA
Co-Authors: Bojovic B; Ha JS; Brown EN; Panda A; Munivenkatappa R; Shipley ST; Rodriguez ED; Bartlett ST; Barth RN
University of Maryland School of Medicine

Introduction: Clinical protocols for vascularized composite allografts (VCA) have included donor bone marrow cell (BMC) infusion after lymphocyte depletion as an immunomodulatory strategy. We previously demonstrated that vascularized bone marrow (VBM) protects facial VCA from rejection in unconditioned nonhuman primates. To investigate the potential benefit of infused BMC, we substituted infused BMC for VBM in the transplanted facial segment.

Methods: Three cynomolgus macaques underwent heterotopic facial segment transplantation with mandibular segment removed, followed by BMC infusion from the same MHC-mismatched donor on postoperative day 1. BMC were infused at 200 million cells per kg recipient weight. Immunosuppression was maintained with tacrolimus and mycophenolate mofetil. Rejection episodes were not treated. Peripheral blood chimerism and CD34+ hematopoeitic stem and progenitor cells were measured using flow cytometry.

Results: Mean cell content of the mandibular segments set aside before transplantation was 48.2 million cells/kg of donor weight. CD34+ cells comprised 5.63% of vertebral bone marrow BMC and 7.60% of mandibular BMC. Animals in the previous VCA+VBM treatment group had no graft loss while on immunosuppression. Graft survival was longer vs. VCA alone (205-430 vs. 9-42 days), as was rejection-free survival (44-358 vs. 7-15 days). In the VCA + BMC group acute rejection was accelerated, occurring in all animals by day 44 (p=0.002). Graft loss occurred more quickly, with longest graft survival 115 days (p=0.007). Only one animal receiving BMC and one receiving VCA alone demonstrated transient macrochimerism. In contrast, 3 of 4 VCA+VBM animals demonstrated macrochimerism.

Conclusions: Despite larger cell counts, BMC infusion failed to prolong facial VCA survival compared to VBM. These data support that VBM is a more effective immunomodulatory strategy than infusion of donor BMC without depletional pre-conditioning. The addition of irradiation and T cell depletion therapies to VBM may enhance proportion and durability of chimerism, and potentially allow for the development of tolerance.


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