Director, Transplant Services
Department / Division
Surgery / Cardiovascular & Thoracic
Durham, NC 27710
Adult cardiac surgery and cardiothoracic transplantation (lung, heart-lung, and heart); coronary artery revascularization, including minimally invasive and hybrid procedures; valve repair and replacement surgery; surgical treatment of chronic thromboembolic pulmonary hypertension and chronic atrial fibrillation
As pulmonary transplantation has evolved into an effective therapy
for end-stage lung disease, the shortage of acceptable donor lung allografts has intensified. Fewer than 20% of patients currently on the waiting list will receive a lung transplant in the coming year; and for every patient who does receive a lung transplant a potential recipient will die. To address this problem, we are evaluating the feasibility of using swine as donors for humans, i.e. lung xenotransplant.
The immunologic barrier to transplantation of widely disparate
species (discordant xenotransplantation) involves natural immunity. In the unmodified model of pig to primate transplantation of heart or kidney, an organ graft is rapidly and violently rejected within minutes to hours. In contradistinction we have shown that the pulmonary xenografts in unmodified recipients had prolonged function. Additionally, whereas histopathologic analysis of heart and kidney xenografts reveals heavy deposition of IgM, C3, C5, and membrane attack complex (MAC), analysis of pulmonary xenografts reveals little IgM and complement deposition. This suggests a lesser immunologic barrier exists to lung xenotransplantation as compared to heart or kidney xenografting.
The purpose of our studies is to define the immunologic barrier to
lung xenotransplantation, and to develop strategies to enable clinical application. We are currently investigating the roles of natural xenoreactive antibody and complement activation in the development of xenograft rejection. These studies are performed using an ex-vivo perfusion model of the swine lung and an in-vivo pig donor to baboon recipient model. A variety of different techniques to deplete xenoreactive antibody and compliment are utilized in these studies. In addition, transgenic swine have been designed to further lessen the immunologic barriers.
These studies are designed to build the foundation for clinical application of xenotransplantation.
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