A vascularized elbow allotransplantation model in the rat

Background: The aim of this research was to develop a rat model for vascularized composite allotransplantation (VCA) of the elbow. Methods: We developed an animal model for VCA of the elbow in rats. Microvascular VCA was performed in 9 rats across a major histocompatibility barrier. Three different immunosuppressive regimens were provided. Joint mobility and weight-bearing capability were assessed throughout 90days of life. Pedicle patency, bone blood flow, and histologic analyses were performed. Results: In the cyclosporine group, forelimb activity was recovered during the postoperative 90days. The extremity that was operated on was used in daily activities. There was minimal motion or use of the limb in the cyclosporine taper and control groups. The vascular pedicles were patent at the time of death in the cyclosporine-treated group but not in the remaining groups. Micro-computed tomography scan performed 3months after transplantation revealed union at the bone junctions, and the elbow joint appeared grossly normal on death in the cyclosporine treatment group only. Incomplete healing was observed in the other 2 groups, and the elbow joints were grossly destroyed. Histologic examination revealed normal cartilage and bone cells in the cyclosporine-treated group, whereas the nontreated groups demonstrated lymphocytic infiltration and loss of normal histologic features. Flow cytometry of blood samples obtained on days 14, 30, 60, and 90 showed no recipient cell chimerism in any of the groups. Conclusions: We developed an animal model for elbow VCA. Immunosuppressed animals regained nearly normal function of forelimbs and maintained grossly normal elbow cartilage. Without cyclosporine treatment, the elbow transplants were rejected.