Research Project
9306494
PROJECT SUMMARY This Phase I program is aimed at achieving high viability and function of insulin secreting cells through sustained O2 delivery to implanted tissues. Giner has successfully demonstrated the benefits of supplemental O2 in the survival and function of pancreatic islets in a densely-packed immunoisolation device. The first proposed application of this platform technology is pancreatic islet implant for the treatment of Type 1 diabetes (T1D). The specific goal is to design and demonstrate an electrochemical O2 generator with passive pressure-limiting capability, implemented as a pressure-differential sensitive cell construction, which limits cell current and gas generation, and achieves fine control over O2 dose, while decreasing size and complexity of the implanted device. The combination of O2 generation with a well-characterized immunoisolation device is termed a bioartificial pancreas with implantable oxygen supply (BAPIOS?). The implantable O2 generator is a platform technology that is amenable to oxygenation of other cellular therapies for conditions such as liver failure, Parkinson?s disease, (para)thyroid disease and hemophilia. Pancreatic islet allotransplantation is in U.S. clinical trials. There are also results from leading centers demonstrating insulin independence for more than 5 years for 50% of the recipients. However, widespread clinical application of for T1D is hindered by two critical barriers: 1) the need for systemic immunosuppression for the current intraportal liver transplant site; and 2) by the finite and low supply of human islet tissue (a few thousand suitable donors per year). The use of biocompatible, retrievable, cell isolating devices may address these critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression and the eventual use of stem cell-derived or xenogeneic islets with minimum or no immunosuppression. Autotransplantation (for pancreatitis patients and pre-cancer diagnosis) could also benefit from a simple implant procedure with retrievability and cellular immunoisolation. Current cell implant devices have insufficient oxygen (even with prevascularization of the device) to provide the high cellular densities required for practically-sized clinical implants. The proposed innovation is a critical advance for Giner?s oxygen generation technology and will enable improved reliability and density of the BAPIOS? implantable cell therapy capsule with continuous oxygen supply. The Specific Aims are: Aim 1: Advance the SREGG from the initial prototype phase to an application-specific device for integration with oxygenated cell capsule and in vitro tests. Aim 2: Fabrication and evaluation of (10) prototype SREGG cells for bioartificial pancreas oxygenation; and Aim 3: Preliminary component and packaging design of clinical SREGG for T1D therapy device. This project will provide the groundwork for final design and fabrication of BAPIOS?-integrated units in Phase II and validation in animal studies, ultimately leading to treatment of T1D in humans.
