ISOLATION AND DISTRIBUTION OF HIGH QUALITY HUMAN PANCREATIC ISLETS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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建立的主要目标是联合多学科科学家和临床医生，将他们的专业知识集中在成功胰岛移植的新策略的开发上。自项目启动以来，已经实现了关键的科学和基础设施里程碑，包括：1)建立一个符合FDA标准的cGMP设施，专门用于胰岛处理；2)招聘和培训有资格进行胰岛分离的人员，并指派专门的移植外科医生进行人体胰腺的现场恢复；3)与当地器官采购组织建立强有力的合作，这导致了死者供体人体胰腺采购的显著增加。4)向从事糖尿病研究的地区和国家科学家分发离体胰岛5)启动T1D患者的临床胰岛移植6)建立基于GCRC的胰岛移植受体代谢评估项目7)基于生化和生理参数制定标准化的胰岛质量指标8)开发创新的免疫治疗方案以诱导对胰岛异体移植的免疫耐受。在目前的提案中，这一强大的基础设施将作为我们的ICR项目进一步发展的机制，以获取人类已故供体胰腺，这将是生产用于移植的临床级胰岛的关键。这一目标将通过从包括非心脏器官供体在内的扩大供体池中采购胰腺来实现。此外，我们将继续回收和分发来自2型糖尿病供体的胰岛，用于2型糖尿病发病机制的生理和基因组研究。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具有专业知识的领先科学家将利用最先进的生物测定技术来开发具有预测价值的胰岛质量指数，在胰岛移植准备之前的决策算法中。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中心共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.