ISLET TRANSPLANTATION-- PROTECTION BY IMMUNOBARRIERS

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DESCRIPTION (Verbatim from Applicant's Abstract): The goal of this proposal is to determine the potential of immunobarrier technology to protect transplanted islets. We hypothesize that there are important differences in what is required for protection against autoimmunity, allorejection and xenorejection. It is expected that genetic manipulation of the encapsulated islets can further reduce damage from these processes. Aim 1. To define the immunobarrier requirements for protection against the separate processes of autoimmunity, allorejection and xenorejection. Alginate microcapsules with and without polylysine coating will be tested for their ability to protect against these different immune mechanisms in mouse recipients. NOD mice will be used to study autoimrnunity. For xenorejection studies, rat islets and porcine neonatal pancreatic cell clusters will be used as a donor source. Aim 2. To improve the outcomes of encapsulated islets with gene transfer approaches. One strategy is to make encapsulated islets better able to resist hypoxic and irnmune injury through the use of the antiapoptotic genes A20 and Bc1-2. The other is to engineer the islets to secrete peptides, in particular CTLA4 and TGF-p, that may modulate the immune attack surrounding the capsules.