The Edmonton experience has demonstrated the possibility of curing Type I diabetes with islet transplantation. These exciting developments have ignited the field and stimulated interest in the examination of various aspects of procurement presentation, and isolation with the aim of optimizing these steps to achieve uniform success with single donor transplants. Our team of clinicians and islet researchers has a long history of experience in the treatment of diabetes by pancreas and pancreas- kidney transplantation and an extensive experience in human islet isolation, preservation and genetic modification of human islets. We have also conducted human islet transplantation in our center, and have participated in multi-center trials for diabetes management. In this proposal we present plans to develop an Islet Resource Laboratory (ICR) that will provide high quality islets for clinic and research use. We also describe a series of process control and standardization, and propose novel strategies aimed at improving the outcome of pancreas procurement, preservation, islet isolation and more reliable viability testing. Moreover, we have established collaborations with colleagues from the Chemistry Department and from the Tullahoma Space Research Institute and the Oak Ridge National Laboratory to redesign the process of islet isolation and transportation. The proposed ICR has several key strengths including (1) the documented success of our islet isolation laboratory and our ability to produce high quality islets; (2) our experience in preserving viable and functional islets for an extended period; (3) our ongoing islet basic research and gene therapy program; (4) the central location of Memphis, and the availability of reliable transportation options (Northwest, Federal Express) to facilitate distribution to various centers; (5) our consortium agreement with several contiguous OPOs that enhances our ability to obtain cadaveric pancreata for isolation; (6) our network of transplants programs interested in receiving islets for clinical use; (7) the large group of unique researchers with experience in chemical and physical sensors, atmospheric control and engineering that are intimately involved in process design; and (8) the University's core resources in genomics proteomics and molecular medicine that will be made available to other ICRs, and finally our history of collaboration with others working in the islet field, We plan to share our findings and experience with other to be established PCRs and are prepared to validate, modify, and standardize our own protocols based on shared data and extensive communication. The overall aims of our application are to (1) optimize and standardize pancreatic procurement and preservation; (2) standardize, optimize and redesign the islet isolation process with the goal of improving islet yield, purity, viability and functionality, as well as to develop reliable methods to predict in vivo functionality of isolated islets; (3) create a network of procurement and distribution sites for clinical islet transplantation; and (4) optimize the preservation and transportation of islets for clinical and research use. These goals are supported by ample experience of the research team, a strong group of consultants, adequate preliminary, and data and by our University's commitment to the field. Our team consists of individuals with multi-disciplinary expertise that combines clinical and basic scientists together with world-recognized technology development experts. This team has worked well together with the aim of curing diabetes through islet transplantation.
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