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Transplantation of organ cultured fetal pig pancreas in non‐obese diabetic (NOD) mice and primates (Macaca fascicularis)

Abstract: Xenografts of organ cultured fetal pig pancreas in prediabetic NOD mice can survive for prolonged periods (>20 weeks) in recipients treated with anti‐T cell monoclonal antibodies (MAb) directed against host CD4 and CD3 cell surface molecules. Anti‐CD4 MAb treatment alone is only partly effective and xenograft rejection occurs over a period of many weeks. In diabetic recipients, by contrast, recurrence of autoimmune disease in isografts is rapid (<28 days) despite similar depletion of CD4+ve T cells. In spontaneously diabetic NOD mice immunosuppressed with anti‐CD3 and anti‐CD4 MAbs xenograft function occurs and the recipient's blood glucose levels fall into the pig range. Organ cultured fetal pig pancreas transplanted into cynomolgus monkeys is rapidly but not hyperacutely rejected when azathioprine‐cyclosporin A‐prednisolone immunosuppression is used. Anti‐T‐cell MAb treatment is now being studied in this primate model.