A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation (VCA) Research

The overall goal of the following experiment is to establish a reliable and reproducible translational large animal model of hind limb transplantation containing an intact vascularized bone marrow for studying immunologic outcomes of clinically relevant immunomodulatory protocols. This is achieved by first harvesting an osteo myocutaneous flap to study the unique immunologic features of the skin component of vascularized composite allo transplantation or VCA together with vascularized bone marrow. Next, the allograft is transplanted to a subcutaneous abdominal wall pocket, which makes it a technically feasible model without hindering the recipient's locomotion.

Then the skin component is exteriorized to the dorsal lateral abdominal wall to monitor the graft by direct visual inspection of the animal in a standing position. The results show that this is a reliable and reproducible model for testing clinically relevant immunomodulatory protocols utilizing cell-based therapies and biologic agents. The main advantage of this technique over existing models such as canine and non-human primate models of VCA is it is more cost effective with the lowest risk of zoonotic infection and the presence of SLA defined donor and recipient strains.