HUMAN PANCREATIC ISLET CELL RESOURCES

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(由申请者提供)：明尼苏达大学胰岛细胞资源(ICR)建立良好。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，致力于按照FDA当前的良好制造规范(CGMP)法规生产生物制品。该中心的工作人员培训了众多访问科学家，自1996年以来准备了420种人类胰岛产品，自1998年以来向77名研究人员运送了250批胰岛(总计约相当于1100万个胰岛)，并生产了33种人类胰岛产品，这些产品被移植到参加4期L/11临床试验的24名1型糖尿病患者体内。在这24名受试者中，有21人在移植后成为非胰岛素依赖者(另外3人中有2人接受了单次胰岛输注)，这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发展和继续ICR，我们提出了以下具体目标：具体目标1：将符合cGMP规定制造和表征的人类胰岛产品分发给符合条件的临床研究人员，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，将人类胰岛产品分发给符合条件的基础科学家进行经批准的实验室研究。具体目标#3：开发评估人类胰岛产品的改进方法，并采用标准化措施来识别可预测临床疗效的此类产品的特征。具体目标4：根据目标3中预期验证的胰岛产品测试，优化胰腺采购、保存和处理程序以及胰岛存储和运输协议。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估进行互动，与ABCC互动，及时向ABCC传输胰岛评估、基础实验室和临床数据，并与指导委员会成员分享可申请专利的概念，以供其他ICR使用，从而支持NCRR ICRS计划的总体使命。拟议工作的成功完成将进一步促进i)人胰岛β细胞生物学、细胞保护、功能、成像、免疫调节、磁性标记、微重力、复制、血运重建、转录和翻译调节、转基因和转导的基础研究以及ii)胰岛移植的安全性和有效性的临床研究。总体而言，拟议的ICR将帮助开发新的和改进的1型和2型糖尿病诊断和治疗方法，从而改善患有这种具有挑战性的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.