FAST LIGAND FOR PROTECTION OF TRANSPLANTED B ISLET CELLS

描述：(改编自申请者摘要)： 在这项申请中提出的研究是生物工程 异体和异种胰岛细胞将被接受为 在制造的生物材料中无封装的植入。 最近的研究表明，Fas配体(FasL)的表达可以诱导 通过刺激Fas+巨噬细胞的凋亡和激活来耐受 T细胞。第一阶段研究的具体目标如下：(1) 确定LPR小鼠的胰岛在GLD中的存活率是否增加 将小鼠与GLD比较成LPR小鼠。(2)确定胰岛细胞是否 来自大鼠的胰岛素启动子-FasL转基因小鼠表现出延长的移植物 生死存亡。(3)确定是否会延长同种异体移植物存活时间 用FasL腺病毒感染的小鼠和人胰岛移植物。 预计这些研究将为第二阶段的工作提供基础 胰岛素调控下人FasL转基因猪的研制 胰岛细胞移植的启动子。商业广告 应用将是现成的胰岛细胞供应 稳定表达Fas的L作为人工胰腺移植 在糖尿病患者中。 建议的商业应用：不可用

DESCRIPTION: (Adapted from the Applicant's Abstract): The goal of the research proposed in this application is the bioengineering of allogeneic and xenogeneic beta islet cells that would be accepted for implantation without encapsulation in a manufactured biomaterial. Recent studies indicate that expression of Fas ligand (FasL) can induce tolerance by stimulation of apoptosis in Fas+ macrophages and activated T cells. Specific Aims of the Phase I research are as follows: (1) Determine if there is increased survival of islets from lpr mice in gld mice compared to gld into lpr mice. (2) Determine if beta islet cells from rat insulin promoter-FasL transgenic mice exhibit prolonged graft survival. (3) Determined if prolonged allograft survival will occur with grafts of mouse and human islets infected with FasL adenovirus. These studies are expected to provide the basis for Phase II work to develop transgenic pigs with human FasL under the control of the insulin promoter for beta islet cell transplantation. The commercial application would be the readily available supply of islet cells with stable Fas L expression for transplantation as an artificial pancreas in patients with diabetes mellitus. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE