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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们最近表明，针对CD28/CD80/CD86和CD40/CD154的cost刺激途径，使用LEA29Y和CHI220延长了恒河猕猴中的同种异体移植存活。 基于这些结果，我们研究了几种替代药物方案以及糖尿病诱导的替代方法。 尽管我们传统上使用十二指肠比较胰腺切除术，但在其他模型中使用了链蛋糕素来产生糖尿病。 链霉菌素比胰腺切除术具有多个优势，包括避免具有相关风险和保留胰腺外分分泌功能的重大操作。 三只动物在CTLA4IG和基于3A8的基于CORTIMUTAUTION BLOCKADE的方案的覆盖下接受了链蛋白酶诱导的糖尿病，随后的同系动物移植。 该队列中的所有接受者在移植后第1天之前都具有立即的同种异体移植功能，并具有对禁食血糖的归一化。 研究已开始确定胰岛移植的最佳解剖部位。 重点已经开始放在胶囊袋上，以评估多个解剖位置，以确定胰岛移植的最佳解剖部位。