ISOLATION AND DISTRIBUTION OF HIGH QUALITY HUMAN PANCREATIC ISLETS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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胰岛移植治疗1型糖尿病的应用感兴趣。宾夕法尼亚大学的综合胰岛移植项目的主要目标是联合一群多学科科学家和临床医生，将他们的专业知识集中在开发成功胰岛移植的新策略上。自该计划开始以来，已经实现了关键的科学和免费基础设施里程碑，其中包括：1）建造符合FDA标准的cGMP设施，专门用于胰岛处理，2）招募和培训有资格进行胰岛分离的人员，并分配专门的移植外科医生用于现场恢复人胰腺，3）与当地器官采购组织建立了强有力的合作关系，这使得已故捐赠者胰腺的采购量显着增加，4）将分离的胰岛分配给从事糖尿病研究的区域和国家科学家5）在T1 D受试者中开始临床胰岛移植6）建立基于GCRC的胰岛移植受体代谢评估程序，7）基于生化和生理参数开发标准化胰岛质量指数，8）开发用于诱导对胰岛同种异体移植物的免疫耐受的创新免疫治疗方案。 在本提案中，这种强大的基础设施将作为我们ICR项目在人类死亡供体胰腺获取方面进一步发展的机制，这对于生产用于移植的临床级胰岛至关重要。这一目标将通过从包括无心跳器官供体在内的扩大供体库中采购胰腺来实现。此外，我们将继续从2型糖尿病供体中回收和分配胰岛，用于2型糖尿病发病机制的生理学和基因组学研究。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具有专业知识的领先科学家将利用最先进的生物测定来开发胰岛质量指数，该指数在胰岛制剂移植之前的决策算法中具有预测价值。宾夕法尼亚大学的ICR项目将继续成为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中心分享我们的临床和基础研究数据，进行合作研究，以推进胰岛加工和移植的生物学。

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.