ISLET TRANSPLANTATION-- PROTECTION BY IMMUNOBARRIERS

描述(逐字摘自申请者摘要)：本提案的目标是 确定免疫屏障技术保护移植的潜力 小岛。我们假设在所要求的内容上有重要的不同 用于预防自身免疫、同种异体排斥和异种排斥。它是 预计对被包裹的胰岛的遗传操作可以进一步 减少这些过程造成的损害。 目标1.确定免疫屏障的要求，以防止 自身免疫、同种异体排斥和异种排斥的过程是分开的。海藻酸盐 带有和不带有聚赖氨酸涂层的微胶囊将被测试其 小鼠对这些不同免疫机制的保护能力 收件人。NOD小鼠将被用于研究自身免疫。用于异种排斥 研究，将使用大鼠胰岛和猪新生胰腺细胞群 作为捐赠者的来源。 目的2.通过基因转移改善包囊化胰岛的结局 接近了。一种策略是使被封装的胰岛更能抵抗 抗细胞凋亡基因A20和A20在缺氧和免疫损伤中的作用 Bc1-2。另一种是改造胰岛，特别是分泌多肽 CTLA4和转化生长因子-β，可能调节胶囊周围的免疫攻击。

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.