HUMAN PANCREATIC ISLET CELL RESOURCES

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）：明尼苏达大学胰岛细胞资源（ICR）已建立。它位于明尼苏达州分子和细胞治疗设施，这是一个36，000平方英尺的设施，专门用于生产符合FDA现行良好生产规范（cGMP）法规的生物制剂。在该ICR工作的工作人员培训了许多访问科学家，自1996年以来制备了420种人类胰岛产品，自1998年以来向77名研究者运送了250种胰岛产品（总计约1100万个胰岛当量），并制造了33种人类胰岛产品，移植到24名参加4项I/II期临床试验的1型糖尿病受试者体内。在这24例受试者中，21例在移植后成为胰岛素非依赖型（另外3例中有2例接受了单次胰岛输注），表明制备高质量胰岛产品的技术已经建立。为了在这些成就的基础上继续ICR，我们提出了以下具体目标：具体目标#1：将人类胰岛产品-按照cGMP法规生产和表征-分发给合格的临床研究者，以获得批准的移植方案。具体目标#2：根据行政和生物信息学协调中心（ABCC）实施的分配算法，将人类胰岛产品分配给合格的基础科学家进行批准的实验室研究。具体目标#3：开发用于评估人类胰岛产品的改进方法，并采用标准化措施来识别此类产品的预测临床疗效的特征。具体目标#4：根据目标3中前瞻性验证的胰岛产品检测，优化胰腺采购、保存和加工程序以及胰岛储存和运输方案。具体目标#5：通过与其他ICR和指导委员会协调活动，与ABCC就计划研究的设计和统计评价进行互动，及时向ABCC传输胰岛评估、基础实验室和临床数据，以及与指导委员会成员分享可专利概念供其他ICR使用，支持NCRR ICR项目的总体使命。拟议工作的成功完成将进一步i）人类胰岛β细胞生物学，细胞保护，功能，成像，免疫调节，磁标记，微重力，复制，血管重建，转录和翻译调控，转染和转导的基础研究以及ii）胰岛移植安全性和有效性的临床研究。总的来说，拟议的ICR将有助于开发1型和2型糖尿病的新型和改进的诊断和治疗方法，从而改善患有这种具有挑战性疾病的人的健康和福祉。

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 University of Minnesota Islet Cell Resource (ICR) is well established. It is located in the Minnesota Molecular and Cellular Therapeutics Facility, a 36,000 sq ft facility dedicated to the manufacture of biologics in compliance with FDA's current Good Manufacturing Practices (cGMP) regulations. Staff working at this ICR has trained numerous visiting scientists, prepared 420 human islet products since 1996, made 250 islet shipments to 77 investigators since 1998 (totaling approximately 11 million islet equivalents), and manufactured 33 human islet products transplanted into 24 type 1 diabetic subjects enrolled in 4 Phase l/ll clinical trials. Of these 24 subjects, 21 became insulin-independent posttransplant (2 of the other 3 received a single islet infusion), indicating that techniques for preparing high-quality islet products are established. To build on these accomplishments and to continue the ICR we propose the following Specific Aims: Specific Aim #1: To distribute human islet products - manufactured and characterized in adherence to cGMP regulations - to eligible clinical investigators for approved transplantation protocols. Specific Aim #2: To distribute human islet products to eligible basic scientists for approved laboratory research studies according to allocation algorithms implemented by the Administrative and Bioinformatics Coordinating Center (ABCC). Specific Aim #3: To develop improved methods for assessment of human islet products and employ standardized measures to identify characteristics of such products that are predictive of clinical efficacy. Specific Aim #4: To optimize pancreas procurement, preservation, and processing procedures as well as islet storage and shipment protocols based on islet product testing prospectively validated in Aim #3. Specific Aim #5: To support the overall mission of the NCRR ICRs Program by coordinating activities with other ICRs and the Steering Committee; interacting with the ABCC on design and statistical evaluation of planned studies; transmitting islet assessment, basic laboratory, and clinical data to the ABCC in a timely manner; and by sharing patentable concepts with the Steering Committee members for use by other ICRs. Successful completion of the proposed work will further i) basic research on human islet beta cell biology, cytoprotection, function, imaging, immunomodulation, magnetic labeling, microgravity, replication, revascularization, transcriptional and translational regulation, transfection and transduction as well as ii) clinical research on the safety and efficacy of islet transplantation. Collectively, the proposed ICR will aid the development of novel and improved diagnostics and therapeutics for type 1 and type 2 diabetes, thereby improving the health and well-being of people afflicted with this challenging disease.