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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们最近发现，针对CD28/CD80/CD86和CD40/CD154共刺激通路，通过使用LEA29Y和Chi220，可以延长猕猴同种异体移植物的存活时间。基于这些结果，我们调查了几种替代药物方案以及诱发糖尿病的替代方法。 虽然我们传统上使用保留十二指肠的胰腺切除术，但链脲佐菌素在其他模型中也用于制造糖尿病。与胰腺切除术相比，链脲佐菌素有几个优点，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。 在CTLA4Ig和3A8共刺激阻断方案的覆盖下，三只动物接受了链脲佐菌素诱导的糖尿病和随后的同种异体胰岛移植。该队列中的所有受者在移植后第一天空腹血糖正常化后立即具有同种异体移植的功能。 研究已经开始确定胰岛移植的最佳解剖位置。焦点已经开始放在大网膜袋上，以评估多个解剖位置，以确定胰岛移植的最佳解剖位置。