Background: Vascularized composite allograft (VCA), such as hand and face allograft, contains a vascularized bone component that may provide an immunologic benefit and induce tolerance for the simultaneous inclusion of marrow cells and a marrow microenvironment. We developed a chimeric groin cutaneous/femur flap to investigate the effect of vascularized bone marrow on VCA survival and its ability to induce chimerism.
Methods: Brown Norway and Lewis rats were used as donors and recipients, respectively. The experimental groups were as follows: groin flap transplantation alone, flap plus intravenous donor bone marrow cells and flap plus simultaneous femur transplantation. Animals received a nonmyeloablative conditioning regimen that consisted of 7-Gy thymic irradiation, 0.75-mL antilymphocyte serum, and 8-mg-1kg-1d cyclosporine A. The flap survival time, peripheral blood chimerism, and the bone marrow of transplanted femurs were analyzed and compared between groups.
Results: Our data showed that the conditioning regimen was effective in T cell ablation. Simultaneous femur transplantation significantly prolonged the median flap survival time (78.8 ± 13.0 d, n = 8) compared with the intravenous bone marrow infusion group (60.9 ± 2.2 d, n = 7) and the control group (58.6 ± 1.3 d, n = 5). Peripheral blood chimerism of 5.81% ± 1.98% was persistently detected for 60 d in recipients of femur transplants but not in the other two groups. Viable bone marrow was confirmed within the transplanted femur on postoperative d 60, but it was gradually replaced by recipient origin cells and eventually developed rejection and fibrosis.
Conclusions: Vascularized bone component plays some protective roles on VCA survival but fails to provide a continuous source of donor cells.
Keywords: Bone marrow transplantation; Chimerism; Immune tolerance; Vascularized bone marrow transplantation; Vascularized composite allotransplantation.
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