Xenotransplantation model for vascularized musculoskeletal tissues in rodents

The purpose of this study was to establish a model and to define the mechan ism of rejection for the transplantation of vascularized musculoskeletal xe nografts between C57BL/6j (B6) mice and Lewis rats. This was accomplished b y using conventional skin xenografts to determine immunologic baseline data between these species and by performing musculoskeletal grafts from the B6 mice transplanted into Lewis rats. After the transplant, the xenografts we re examined histologically and the recipients were assessed for immune reac tion using in vitro assays to measure both cell-mediated and humoral respon ses. The results obtained from the skin xenografts showed activation of bot h cellular and humoral immunologic responses. All musculoskeletal xenograft s were rejected between 3 and 4 postoperative days. Histologically, the gra fts showed extensive vascular injury manifested by thrombosis and hemorrhag e, suggesting an early humoral response. Anti-donor antibody production was detected in the recipient's sera soon after rejection of the xenogeneic ti ssue. The cell-mediated immune response, although detectable by the in vitr o assays, was less pronounced than the humoral response and corroborated th e histologic findings of mild lymphocyte infiltration in the rejected tissu e. These results demonstrate that humoral rejection plays a predominant rol e in the rejection of vascularized musculoskeletal xenotransplants between concordant species. This mouse-to-rat vascularized xenograft model will be utilized for further studies on inducing tolerance to vascularized musculos keletal xenografts. (C) 2000 Wiley-Liss, Inc.