ISOLATION AND DISTRIBUTION OF HIGH QUALITY HUMAN PANCREATIC ISLETS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。描述(由申请人提供)：宾夕法尼亚大学的移植项目长期以来一直对应用胰岛移植治疗1型糖尿病感兴趣。宾夕法尼亚大学建立了全面的胰岛移植计划，主要目标是联合一群多学科的科学家和临床医生，将他们的专业知识集中在开发成功的胰岛移植的新策略上。自该计划开始以来，已经取得了关键的科学和免费基础设施里程碑，包括：1)建立了专门用于胰岛处理的符合FDA的cGMP设施，2)招聘和培训了有资格进行胰岛分离的人员，并指派了专职的移植外科医生就地恢复人胰腺，3)与当地器官采购组织建立了强有力的合作，导致对已故捐赠者胰腺的采购显著增加，4)向从事糖尿病研究的地区和国家科学家分发孤立的胰岛5)在T1D受试者中启动临床胰岛移植6)建立基于GCRC的计划，用于胰岛移植受者的代谢评估，7)开发基于生化和生理参数的标准化胰岛质量指数；8)开发创新的免疫治疗方案，以诱导同种异体胰岛移植物的免疫耐受。在目前的提议中，这一强大的基础设施将作为我们的ICR计划在获取人类已故供体胰腺方面进一步增长的机制，这将是生产临床级移植胰岛的关键。这一目标将通过从包括非心脏跳动器官捐赠者在内的扩大的捐赠者池中购买胰腺来实现。此外，我们将继续从2型糖尿病捐赠者那里回收和分发胰岛，用于2型糖尿病发病机制的生理学和基因组研究。重要的是，在胰岛生物化学、功能基因组学、蛋白质组学和胰岛发育和新生方面拥有专业知识的领先科学家将利用最先进的生物检测手段，在胰岛制剂移植前的决策算法中开发具有预测价值的胰岛质量指数。宾夕法尼亚大学的ICR项目将继续是指导委员会的积极成员；利用ABCC的生物信息学资源，我们将与其他ICR中心共享我们的临床和基础研究数据，进行协作研究，以促进胰岛加工和移植的生物学研究。

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. DESCRIPTION (provided by applicant): The transplant program at the University of Pennsylvania has had a long standing interest in the application of pancreatic islet transplantation for treatment of type 1 diabetes mellitus. The comprehensive islet transplantation program at the University of Pennsylvania was established with the primary objective of uniting a group of multidisciplinary scientists and clinicians to focus their expertise on the development of novel strategies for successful islet transplantation. Since the inception of the program critical scientific and complimentary infrastructure milestones have been achieved that include: 1) construction of an FDA compliant cGMP facility devoted exclusively to islet processing, 2) recruitment and training of personnel qualified to perform islet isolation and assignment of dedicated transplant surgeons for on-site recovery of human pancreas, 3) establishment of a strong collaboration with the local organ procurement organization which has led to marked increase in the procurement of deceased donor human pancreas, 4) distribution of isolated pancreatic islets to regional and national scientist engaged in diabetes research 5) initiation of clinical islet transplantation in T1D subjects 6) establishment of a GCRC based program for metabolic evaluation of islet transplant recipients, 7) development of a standardized islet quality index based on the biochemical and physiological parameters, 8) development of innovative immunotherapy protocols for induction of immunological tolerance to islet allografts. In the present proposal this strong infrastructure will serve as the mechanism for further growth of our ICR program in the acquisition of human deceased donor pancreas which will be critical for production of clinical grade islets for transplantation. This goal will be accomplished by procurement of pancreas from an expanded donor pool including non-heart beating organ donors. In addition we will continue to recover and distribute islets from type 2 diabetic donors for physiologic and genomic investigations into the pathogenesis of type 2 diabetes. Importantly, the leading scientists with expertise in the islet biochemistry, functional genomics, proteomics and islet development and neogenesis will utilize state of the art bioassays to develop an islet quality index with predictive value in the decision making algorithm prior to transplantation of the islet preparation. The ICR program at Penn will continue to be an active member of the steering committee; utilizing the bioinformatics resources of the ABCC, we will share our clinical and basic research data with other ICR centers for collaborative investigations to advance the biology of islet processing and transplantation.