Heart and en-bloc thymus transplantation in miniature swine

BackgroundDonor-specific tolerance to organ allografts might be induced by cotransplantation of a sufficient amount of vascularized donor thymus. To facilitate donor thymus-induced cardiac allograft tolerance, we have developed a novel technique for heart and en-bloc thymus transplantation in swine.MethodsDonor heart and en-bloc thymus grafts were prepared by a technique that preserves the entire arterial supply and venous drainage of the right thymic lobe. En-bloc grafts (n = 4) were transplanted heterotopically into the abdomens of major histocompatibility complex-matched miniature swine. Recipients received 12 days of cyclosporine intravenously. Grafts were monitored by palpation, electrocardiographic monitoring, and periodic open biopsy. Engraftment of the donor thymus was demonstrated by measuring the proportion of recipient-type thymocytes in the donor thymus with flow cytometry.ResultsAll of the heart and en-bloc thymus grafts had normal cardiac contractility and immediate perfusion of the thymus. All en-bloc grafts were accepted for more than 200 days without significant acute cellular rejection or cardiac allograft vasculopathy. Thymic tissue of en-bloc grafts displayed normal architecture and supported thymopoiesis of recipient-type cells.ConclusionWe have validated a new technique of donor thymus transplantation that could have utility in human heart transplantation

Factibilidad del xenotrasplante

El estudio de xenotrasplante como modalidad terap\ue9utica viable para la enfermedad cardiaca en etapa terminal se ha convertido en un campo excitante. Los progresos en la biolog\ueda de la clonaci\uf3n de transferencia nuclear logrados en los \ufaltimos a\uf1os han impulsado a este campo con la creaci\uf3n de un grupo de cerdos clonados en los que se han suprimido ciertos genes. lo que ha tenido como consecuencia cerdos m\ue1s "humanizados'. Adem\ue1s. han tenido buenos resultados ciertas nuevas estrategias para inducir tolerancia inmunitaria contra los ant\uedgenos xenogeneicos en peque\uf1os modelos animales. En plazo muy breve se estar\ue1n trasplantando \uf3rganos de cerdos con deleci\uf3n clonados en receptores primates no humanos (que actuar\uedan como seres humanos sustitutivos) que se han condicionado para inducir tolerancia. De los resultados de estos experimentos depender\ue1 que se vuelva posible el xenotrasplante en el futuro cercano