ISLET TRANSPLANTATION

I型或胰岛素依赖型糖尿病(IDDM)是一种主要的健康问题 有问题。严重的胰岛素缺乏是疾病过程的标志。 分离的胰岛移植是一项实验。 程序，目的是为IDDM提供内源性 胰岛素的来源。越来越多的证据表明临床胰岛 人的胰岛移植。因此，其他方法，如 从亲缘关系密切的动物物种中制备胰岛 猴子，将不得不被探索作为一种替代的捐献组织来源。 BB/W大鼠是一种重要的1型糖尿病动物模型 具有与临床综合征相同的特征，如胰腺炎、 酮症酸中毒，严重的高血糖与B细胞的破坏有关。 胰岛自体移植的早期研究进展 糖尿病BB/W大鼠表现为：1)同种异体胰岛移植物无限期存活 可以在没有持续免疫抑制的情况下实现，前提是 胰岛被注射到免疫特权的腹部睾丸中。 2)胰岛素测定作为检测活B细胞的工具表明 移植到睾丸内的胰岛保存良好。3)学习 关于睾丸免疫豁免机制的研究表明， 睾丸激素和黄体酮都是导致这种显著症状的因素。 腹部睾丸内、胰岛同种异体移植物的存活。4)扩展 BB/W大鼠睾丸内异种胰岛移植存活的可能性 用环孢素A。 我们现在建议，作为我们的第一个目标，研究长期小岛的去向。 在免疫抑制停止后，同种异体移植物的存活取决于 诱导宿主对胰岛抗原的耐受性。作为第二个目标，我们 将继续探索抑制素等因素，由Sertoli产生 细胞，这可能是调节睾丸免疫豁免的细胞。作为第三个目标， 睾丸内同种异体胰岛移植对两者α细胞功能的影响 将对内源性胰腺和移植物进行检查。作为第四个 目的我们计划将移植模型应用于心脏移植。 整合异种移植到更高级的动物，如猴子。这些 研究可能会为移植现象提供新的见解 耐受性，可能对临床胰岛有实际意义 异种移植。

Type I or insulin dependent diabetes mellitus (IDDM) is a major health problem. Severe insulin deficiency is the hallmark of the disease process. The transplantation of isolated pancreatic islets is an experimental procedure with the objective of providing the IDDM with an endogenous source of insulin. Evidence is accumulating that clinical islet transplantation of human islets. Thus other approaches, such as the preparation of islets from a closely related animal species, such as the monkey, will have to be explored as an alternative source of donor tissue. The BB/W rat is an important animal model of type 1 diabetes which has many features in common with the clinical syndrome, such as insulitis, ketoacidosis, and severe hyperglycemia associates with B-cell destruction. Our earlier studies on the transplantation of islets into the spontaneously diabetic BB/W rat have shown that: 1) Indefinite islet allograft survival can be achieved without sustained immunosuppression provided that the islets are injected into the immunologically privileged abdominal testis. 2) Insulin determination as a tool for detecting viable B-cells indicate excellent preservation of islets transplanted into the testis. 3) Studies on the mechanisms of testicular immune privilege suggest that neither testosterone nor progesterone is the factor responsible for the remarkable survival of abdominal intratesticular, islet allografts. 4) Extended survival of intratesticular islet xenografts is possible in the BB/W rat with cyclosporine. We propose now as our first aim to examine whither long-term islet allograft survival, after immunosuppression is stopped, depends on the induction of tolerance in the host to islet antigen. As a second aim we will continue to explore factors such as inhibin, produced by the Sertoli cell, that might mediate testicular immune privilege. As the third aim the effect of intratesticular islet allografts on alpha cell function of both the endogenous pancreas and of the graft will be examined. As the fourth aim we plan to apply the transplantation model towards the grafting of concordant xenografts into a higher animal such as the monkey. These studies might provide new insight into the phenomenon of transplantation tolerance, and might have practical implications for clinical islet xenotransplantation.