Effect of the vascularized bone components on the survival of vascularized composite allografts

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(-1)kg(-1)d 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. (C) 2017 Elsevier Inc. All rights reserved.