STRATEGIES FOR LARGE SCALE ISLET REPLACEMENT

大规模胰岛置换策略

• 批准号: 7715807
• 负责人: THOMAS C PEARSON
• 金额: $ 3.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715807
• 关键词: Allografting; Anatomic Sites; Anatomy; Animals; Biological Preservation; Blood Glucose; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Fasting; Funding; Grant; Institution; Islets of Langerhans Transplantation; LEA29Y; Location; Macaca mulatta; Methods; Modeling; Operative Surgical Procedures; Pancreas; Pancreatectomy; Pathway interactions; Pharmaceutical Preparations; Research; Research Personnel; Resources; Risk; Source; Streptozocin; Transplantation; Treatment Protocols; United States National Institutes of Health; base; cohort; day; islet

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We recently showed that targeting the CD28/CD80/CD86 and CD40/CD154 costimulatory pathways, by using LEA29Y and Chi220, prolongs allograft survival in rhesus macaques. Based on these results, we investigated several alternative drug regimens as well as alternative methods of diabetes induction. While we traditionally use the duodenal-sparing pancreatectomy, streptozotocin is used in other models to produce diabetes. Streptozotocin has several advantages over pancreatectomy including the avoidence of a major operation with its associated risks and preservation of the exocrine function of the pancreas. Three animals underwent diabetes induction with streptozotocin and subsequent alloislet transplant under cover of a CTLA4Ig and 3A8 costimulation blockade-based regimen. All recipients in this cohort have had immediate allograft function with normalization of fasting blood sugars by day 1 post-transplant. Studies have begun to determine the optimal anatomic site for islet transplantation. Focus has begun on an omental pouch to evaluate multiple anatomic locations to determine the optimal anatomic site for islet transplant.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们最近表明，通过使用 LEA29Y 和 Chi220 靶向 CD28/CD80/CD86 和 CD40/CD154 共刺激途径，可以延长恒河猴同种异体移植物的存活时间。 基于这些结果，我们研究了几种替代药物疗法以及诱导糖尿病的替代方法。 虽然我们传统上使用保留十二指肠的胰腺切除术，但链脲佐菌素也用于其他模型来产生糖尿病。 链脲佐菌素比胰腺切除术有几个优点，包括避免大手术及其相关风险以及保留胰腺的外分泌功能。 三只动物用链脲佐菌素进行糖尿病诱导，并在 CTLA4Ig 和 3A8 共刺激阻断方案的掩护下进行随后的同种异体移植。 该队列中的所有受者均立即具有同种异体移植功能，移植后第 1 天空腹血糖正常化。 研究已开始确定胰岛移植的最佳解剖部位。 人们已经开始关注网膜袋，以评估多个解剖位置，以确定胰岛移植的最佳解剖位置。