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. ? ? ?
|Loganathan, Gopalakrishnan; Graham, Melanie L; Radosevich, David M et al. (2013) Factors affecting transplant outcomes in diabetic nude mice receiving human, porcine, and nonhuman primate islets: analysis of 335 transplantations. Transplantation 95:1439-47|
|Kaddis, John S; Hanson, Matthew S; Cravens, James et al. (2013) Standardized transportation of human islets: an islet cell resource center study of more than 2,000 shipments. Cell Transplant 22:1101-11|
|Avgoustiniatos, Efstathios S; Scott 3rd, William E; Suszynski, Thomas M et al. (2012) Supplements in human islet culture: human serum albumin is inferior to fetal bovine serum. Cell Transplant 21:2805-14|
|Bellin, M D; Barton, F B; Heitman, A et al. (2012) Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. Am J Transplant 12:1576-83|
|Balamurugan, A N; Loganathan, Gopalakrishnan; Bellin, Melena D et al. (2012) A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products. Transplantation 93:693-702|
|Loganathan, Gopalakrishnan; Dawra, Rajinder K; Pugazhenthi, Subbiah et al. (2011) Insulin degradation by acinar cell proteases creates a dysfunctional environment for human islets before/after transplantation: benefits of ?-1 antitrypsin treatment. Transplantation 92:1222-30|
|Anazawa, Takayuki; Matsumoto, Shuichiro; Yonekawa, Yukihide et al. (2011) Prediction of pancreatic tissue densities by an analytical test gradient system before purification maximizes human islet recovery for islet autotransplantation/allotransplantation. Transplantation 91:508-14|
|Loganathan, G; Dawra, R K; Pugazhenthi, S et al. (2010) Culture of impure human islet fractions in the presence of alpha-1 antitrypsin prevents insulin cleavage and improves islet recovery. Transplant Proc 42:2055-7|
|Scott 3rd, W E; O'Brien, T D; Ferrer-Fabrega, J et al. (2010) Persufflation improves pancreas preservation when compared with the two-layer method. Transplant Proc 42:2016-9|
|Kaddis, J S; Danobeitia, J S; Niland, J C et al. (2010) Multicenter analysis of novel and established variables associated with successful human islet isolation outcomes. Am J Transplant 10:646-56|
Showing the most recent 10 out of 34 publications