ISLET TRANSPLANTATION

胰岛移植

• 批准号: 3243481
• 负责人: HELENA P SELAWRY
• 金额: $ 10.12万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3243481
• 关键词: B lymphocyte; Sertoli cells; T lymphocyte; diabetes mellitus therapy; glucagon; glucose tolerance test; histocompatibility; homologous transplantation; hormone metabolism; immune tolerance /unresponsiveness; immunosuppression; inhibin; insulin; insulin dependent diabetes mellitus; laboratory rat; pancreatic islet transplantation; xenotransplantation

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.

I型或胰岛素依赖型糖尿病（IDDM）是一种主要的健康问题， 问题. 严重的胰岛素缺乏是疾病过程的标志。 离体胰岛移植是一种实验性的 目的是为胰岛素依赖型糖尿病提供内源性 胰岛素的来源 越来越多的证据表明， 人类胰岛移植。 因此，其他方法，如 从密切相关的动物物种制备胰岛，例如 猴子，将不得不探索作为供体组织的替代来源。 BB/W大鼠是一种重要的1型糖尿病动物模型， 与临床综合征共同的特征，如胰岛炎， 酮症酸中毒和严重的高血糖症与B细胞破坏有关。 我们早期关于胰岛移植到自发性 糖尿病BB/W大鼠显示：1）不确定的胰岛移植物存活 不需要持续的免疫抑制， 将胰岛注射到免疫豁免的腹部睾丸中。 2)胰岛素测定作为检测活B细胞的工具表明 移植到睾丸中的胰岛保存良好。 3)研究 睾丸免疫豁免机制的研究表明， 睾丸激素和孕酮都不是导致 腹部睾丸内胰岛同种异体移植物的存活率。 4)扩展 BB/W大鼠睾丸内胰岛异种移植物的存活是可能的 环孢霉素 我们现在建议，作为我们的第一个目标，检查长期的岛屿 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 将继续探索因素，如塞尔托利生产的 细胞，可能介导睾丸免疫豁免。 作为第三个目标， 同种异体睾丸内胰岛移植对大鼠睾丸α细胞功能影响 将检查移植物的内源性胰腺。 为第四个 我们计划将移植模型应用于 移植到高等动物如猴子体内的异种器官。 这些 这些研究可能会为移植现象提供新的见解， 耐受性，并可能对临床胰岛 异种移植