Diabetes is the 4th leading cause of death in the United States with more than 3 million Americans currently suffering from type 1 diabetes. An average of 80 people per day is diagnosed with the disease, with half of those being children, and presently there is no cure. The primary treatment of type 1 diabetes is the delivery of artificial insulin via injection or pump combined with careful monitoring of blood glucose levels using blood- testing monitors. Transplantation of functional islet tissue by the "Edmonton Protocol" restores euglycemia but requires lifelong pharmaceutical immune suppression, which increases risk of infections and cancer. Thus the Edmonton Protocol is suited for the most "fragile" patients. Encapsulation of islet tissue, which prevents direct contact with the host's immune system, may circumvent pharmaceutical immune suppression, and allow use of xenograft tissue, which is in great supply compared to human. Microencapsulation presents new challenges, specifically hypoxia and poor molecular transport critical to islet function viability. Logic dictates that a pre- vascularized tissue should solve these problems. Unfortunately, the several-day lag between implantation and anastomosis as well as the low density of perfused vessels creates a hypoxic environment that ultimately leads to islet tissue necrosis. It is our premise that revascularization is insufficient, and that islets should be implanted into a device that is already perfused without damaging the microcirculation. In this training program the trainee will investigate a strategy for using only autologous materials to promote a dense perfused vasculature prior to the introduction of xenograft islet tissue. Several features render this project particularly suitable for the F32 mechanism. (1) The trainee's sponsor Dr. Jonathan Lakey was a member of the team that pioneered the "Edmonton Protocol", a popular method for clinical islet transplantation. Dr. Lakey is the Director of the Clinical Islet Program and the Director of Research for the Department of Surgery at UC Irvine. (2) Co-sponsor Dr. Botvinick has founded a venture- funded medical device company for the continuous monitoring of blood glucose. Dr. Botvinick has extensive knowledge in device manufacturing which will be of critical importance in the trainees'project. (3) A mentoring team has been assembled which includes Dr. Bruce Tromberg, director of the Beckman Laser Institute (BLI), Dr. Stuart Nelson, the clinical director of the BLI and Dr. Abe Lee, the founding director of UC Irvine's nano/micro fabrication center. Together we will offer the trainee unparalleled training in device fabrication, animal models of diabetes, physiology of the subcutaneous vasculature, and non-invasive optical interrogation of implanted devices. The mentoring team will guide the trainee in this high impact and multidisciplinary approach toward the reversal of type 1 diabetes.

Public Health Relevance

Diabetes is the 4th leading cause of death in the United States and currently there is no cure. Our aim is to advance treatment of diabetes by making the process automatic, much like a second pancreas specific to insulin delivery where islets are housed in a well-vascularized environment where they remain viable and functional. The advancements of this project can directly translate into human trials and, eventually, the clinic relatively easily and cost-effectively.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-R (M1))
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Castle, Arthur
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University of California Irvine
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United States
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