FAST LIGAND FOR PROTECTION OF TRANSPLANTED B ISLET CELLS

描述：（改编自申请人的摘要）： 本申请中提出的研究是生物工程， 同种异体和异种β胰岛细胞， 植入而不包封在制造的生物材料中。 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 T细胞。第一阶段研究的具体目标如下：（1） 确定在gld中lpr小鼠胰岛的存活率是否增加 小鼠与GLD小鼠相比转化为LPR小鼠。 (2)确定β胰岛细胞 从大鼠胰岛素启动子-FasL转基因小鼠表现出延长的移植 生存 (3)确定是否会发生移植物存活延长 用FasL腺病毒感染的小鼠和人类胰岛移植。 预计这些研究将为第二阶段工作提供基础， 在胰岛素的控制下培育具有人FasL的转基因猪， β胰岛细胞移植的启动子。 商业 应用将是胰岛细胞的容易获得的供应， 稳定表达Fas L人工胰腺移植研究 在糖尿病患者中。 拟议商业应用：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