MODIFICATION OF PORCINE ISLETS FOR TRANSPLANTATION

该项目的目标是提高性能和生存 胰岛素生成细胞，这样它们就可以移植到患有 糖尿病 重点是猪胰岛， 被改造以抵抗异种移植排斥。 其目标是： 1.使用猪新生胰腺细胞簇（NPCCs）学习 更多关于前体和原分化的胰腺细胞 发育成成熟的内分泌细胞。 2.为了操纵复制和分化， 分化因素，以优化组织来源， 移植和增强基因转移策略。 3.为了检查移植到猪的新生细胞群， 裸鼠，以了解其生长能力，分化和 体内功能 4.研究腺病毒载体介导的基因特性 在移植的胰岛中转移和表达，并建立和 表征用于胰岛的基于慢病毒的基因转移系统。 用大鼠胰岛进行的实验代表了实验的前奏 成年和新生猪胰岛。 5.为了确定大鼠胰岛工程表达的程度， CTLA4Ig或FasL在异种移植物中显示出增强的移植物存活， 小鼠糖尿病模型，并表征转基因的要求 表达和参与移植物存活的免疫机制。 6.建立新生儿有效转导的条件， 猪胰岛细胞，以便可以在异种模型中进行研究。

The goal of this project is to improve the performance and survival of insulin producing cells so they can be transplanted into people with diabetes. The focus is upon porcine islets which will be genetically modified to resist xenograft rejection. The aims are: 1. To use porcine neonatal pancreatic cell clusters (NPCCs) to learn more about how precursor and protodifferentiated pancreatic cells develop into mature endocrine cells. 2. To manipulate replication and differentiation with various growth and differentiation factors to both optimize the tissue source for the transplantation and enhance gene transfer maneuvers. 3. To examine populations of porcine neonatal cells transplanted into nude mice to understand their growth capacity, differentiation and function in vivo 4. To study the characteristics of adenovirus vector-mediated gene transfer and expression in transplanted islets and to establish and characterize a lentivirus-based gene transfer system for islets. Experiments performed with rat islets represent a prelude to experiments with adult and neonatal porcine islets. 5. To determine the extent to which rat islets engineered to express either CTLA4Ig or FasL show enhanced graft survival in a xenogeneic mouse diabetes model and to characterize the requirements for transgene expression and the immune mechanisms involved in graft survival. 6. To establish conditions for the efficient transduction of neonatal porcine islet cells so they can be studied in xenogeneic models.