Tolerance Induction to Porcine Islet Xenografts

目前对糖尿病的治疗包括饮食、药物和胰岛素治疗。虽然这些对一些成人发病的糖尿病是令人满意的，但很明显，在青少年糖尿病中，在小心胰岛素剂量的情况下，疾病可能会发展。很明显，整个胰岛作为一个功能单元很可能对糖尿病有最好的控制，当患者移植来自人类供体的整个或部分胰腺时，不仅糖尿病状况得到改善，血管病变也得到改善。因此，移植为糖尿病患者提供了一种新的治疗方法，可以逆转他们的疾病，改善眼睛、肾脏和血管的严重副作用。然而，移植带来了一个问题，即根本没有足够的人类胰岛可用于器官或胰岛移植，因此，正在研究动物作为胰岛的可能来源。这被称为异种移植或异种移植。在所有动物物种中，猪是最合适的供体，原因有很多，例如，猪的血糖控制与人类相似。这项研究的最终目的是研究可能的基因改造，从而生产出转基因猪胰岛，用于移植到人类身上，以治疗糖尿病。本研究的重点是利用小鼠模型阐明最佳组合。重要的是，这项研究将建立原理证明，并提供有关基因的信息，这些信息将有助于最终对临床使用的猪进行基因改造。

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.