Jianwu Chen1, Dongliang Zhang2, Tao Zhang3, Chen Chen2, Yajuan Song2, Shiqiang Liu2, Yingjun Su4, Shuzhong Guo4. 1. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Plastic Surgery, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, China. 2. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. 3. Department of pharmacy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Xi'an, Shaanxi, China. 4. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: xjzxips@163.com.
Abstract
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.
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.