ISLET TRANSPLANTATION-- PROTECTION BY IMMUNOBARRIERS

胰岛移植——免疫屏障的保护

• 批准号: 6699611
• 负责人: Gordon Campbell Weir
• 金额: $ 29.14万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-10 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6699611
• 关键词: CD28 molecule; Lentivirus; NOD mouse; apoptosis; artificial membranes; autoimmunity; biomaterial development /preparation; gene expression; genetically modified animals; homologous transplantation; hypoxia; immune tolerance /unresponsiveness; immunoregulation; laboratory mouse; laboratory rat; membrane permeability; microcapsule; pancreatic islet function; pancreatic islet transplantation; polylysine; tissue /cell culture; transfection /expression vector; transforming growth factors; transplant rejection; xenotransplantation

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.

描述（来自申请人摘要的逐字逐句）：本提案的目标是 以确定免疫屏障技术保护移植的 小岛我们假设在所需的条件上存在重要的差异 用于保护免受自身免疫、同种异体排斥和异种排斥。是 预期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.定义免疫屏障要求以保护免受 自身免疫、同种异体排斥和异种排斥的独立过程。海藻酸 将测试具有和不具有聚赖氨酸涂层的微胶囊的 保护小鼠免受这些不同免疫机制的能力 受惠人士NOD小鼠将用于研究自身免疫。对于异种排斥 研究中，将使用大鼠胰岛和猪新生胰腺细胞簇 作为捐赠来源。 目标二。通过基因转移改善微囊化胰岛的结局 接近。一种策略是使被包裹的胰岛能够更好地抵抗 缺氧和免疫损伤通过使用抗凋亡基因A20和 公元前1 -2。另一个是设计胰岛分泌肽， CTLA 4和TGF-β，其可以调节胶囊周围的免疫攻击。