STRATEGIES FOR LARGE SCALE ISLET REPLACEMENT

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们最近发现，通过使用LEA 29 Y和Chi 220靶向CD 28/CD 80/CD 86和CD 40/CD 154共刺激通路，可以提高恒河猴同种异体移植物的存活率。 基于这些结果，我们研究了几种替代药物方案以及替代糖尿病诱导方法。 虽然我们传统上使用保留胰腺的胰腺切除术，但在其他模型中使用链脲佐菌素来产生糖尿病。 与胰腺切除术相比，链脲佐菌素有几个优点，包括避免了大手术及其相关风险，并保留了胰腺的外分泌功能。 三只动物在CTLA 4 Ig和3A 8共刺激阻断的基础上进行了链脲佐菌素诱导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1天具有立即的同种异体移植物功能，空腹血糖正常化。 研究已经开始确定胰岛移植的最佳解剖部位。 重点已经开始在网膜袋，以评估多个解剖位置，以确定最佳的解剖部位胰岛移植。

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.