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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Materials Resource Cooperative Agreements (U42)
Project #
2U42RR016600-06
Application #
7171964
Study Section
Special Emphasis Panel (ZRR1-CR-1 (01))
Program Officer
Rosenblum, Daniel
Project Start
2001-09-27
Project End
2009-07-31
Budget Start
2006-09-30
Budget End
2007-07-31
Support Year
6
Fiscal Year
2006
Total Cost
$916,915
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Li, Changhong; Liu, Chengyang; Nissim, Itzhak et al. (2013) Regulation of glucagon secretion in normal and diabetic human islets by ?-hydroxybutyrate and glycine. J Biol Chem 288:3938-51
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
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Rickels, Michael R; Mueller, Rebecca; Teff, Karen L et al. (2010) {beta}-Cell secretory capacity and demand in recipients of islet, pancreas, and kidney transplants. J Clin Endocrinol Metab 95:1238-46
Bhandare, Reena; Schug, Jonathan; Le Lay, John et al. (2010) Genome-wide analysis of histone modifications in human pancreatic islets. Genome Res 20:428-33
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
Soleimanpour, Scott A; Crutchlow, Michael F; Ferrari, Alana M et al. (2010) Calcineurin signaling regulates human islet {beta}-cell survival. J Biol Chem 285:40050-9
Deng, Shaoping; Markmann, James F; Rickels, Micheal et al. (2009) Islet alone versus islet after kidney transplantation: metabolic outcomes and islet graft survival. Transplantation 88:820-5

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