Tolerance Induction to Porcine Islet Xenografts

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The current treatment for diabetes involves diet, drugs and insulin treatment. While these are satisfactory for some adult onset diabetes, it is clear that in juvenile diabetes, the disease can progress in the presence of careful insulin dosage. It is apparent that the whole islet as a functional unit is likely to give the best control of diabetes, as when patients are transplanted with whole or segments of pancreas from human donors, as not only is there an improvement in their diabetic status, the vessel lesions improve. Transplantation therefore offers a new therapy to diabetic patients for reversal of their disease and improvement in the serious side affects found in the eye, kidney and blood vessels. However, transplantation introduces a problem in that there is simply not sufficient human islets available for organ or islet transplantation, and in this light, animals are being examined as a possible source of islets. This is called xenografting or xenotransplantation. Of all the animal species, the pig is the most suitable donor for a variety of reasons, for example similar control of blood sugar to humans. The ultimate aims of the study are to examine possible genetic modifications that would allow the production of transgenic pig islets for transplantation to humans for the treatment of diabetes. The focus of the proposed studies is to elucidate the optimal combinations using mouse models. Importantly this study will establish the proof of principle and provide information on the genes that will be useful to finally genetically modify pigs for clinical use.