ALLOGRAFTING OF ADULT ISLETS AFTER IN VITRO MODIFICATION

体外修饰后的成年胰岛同种异体移植

• 批准号: 3236343
• 负责人: ORION D HEGRE
• 金额: $ 11.3万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236343
• 关键词: autoimmune disorder; diabetes mellitus therapy; disease /disorder model; drug related diabetes mellitus; genetic strain; guinea pigs; histochemistry /cytochemistry; homologous transplantation; immunocytochemistry; insulin dependent diabetes mellitus; laboratory mouse; laboratory rabbit; laboratory rat; major histocompatibility complex; nephrectomy; pancreatic islet function; pancreatic islet transplantation; radioimmunoassay; tissue /cell culture; tissue donors

The proposal represents a continuation of our research in the area of islet cell culture and transplantation. The work is intended to serve as a basis for the eventual application of islet cell transplantation in Type 1 diabetes. Experiments involve the investigation of a unique method for the production of non- immunogenic islets from adult rodent sources. These islets can be transplanted without any form of immunosuppression across major histocompatibility barriers. Further understanding of the mechanism by which altered immunogenicity is attained will be pursued. Methods of selective cell culture in which cells necessary for immune recognition can be controlled in vitro will also be explored. In addition, experimental animal models of human Type 1 diabetes of both immunological as well as chemical etiology will be examined to assess the utility of the technologies developed in the reversal of these hyperglycemic-insulinopenic syndromes. The approach centers on the acquisition of morphological data, coupled with biochemical and physiological studies. Techniques of immunoassay, morphometric analysis at the ultrastructural and light microscopical levels, immunocytochemistry, spectrophotometry, chromatography, enzymology, tissue culture, transplantation, and tissue culture permit the correlation of morphological, biochemical and physiological parameters. Major questions remain as barriers to human islet cell transplantation. Can efficient methods be developed for the isolation and purification of human islets? Can methods be developed permitting the purification of islet endocrine grafts circumventing rejection without the need for patient immunosuppression? Will the etiology of Type 1 diabetes be reexpressed in the transplanted grafts thus compromising their function? If so, does the reexpression of the syndrome relate to the immunological similarity between host and donor - can mismatching (allografts) circumvent the autoimmune phenomenon. It is hoped that experiments outlined in this proposal will provide basic research which may lead to the answers to some of these questions.

这项建议代表了我们在该领域研究的继续。 胰岛细胞培养和移植。这项工作的目的是 为胰岛细胞的最终应用奠定基础 1型糖尿病的移植治疗。实验涉及到 一种独特的非金属氧化物生产方法的研究 来自成年啮齿动物来源的免疫原性胰岛。这些小岛可以是 在没有任何形式免疫抑制的情况下移植到 组织相容性障碍。对新世纪的认识 获得改变的免疫原性的机制将是 被追捕。一种细胞选择性培养的方法 需要免疫识别才能在体外控制意志 也是被探索的。此外，实验动物模型 人类1型糖尿病既有免疫性也有化学性 将对病因学进行检查，以评估技术的实用性 在这些高血糖-胰岛素减少的逆转中发展起来的 综合症。 该方法以获取形态数据为中心， 再加上生化和生理学研究。技术问题 免疫分析，超微结构和形态计量学分析 光镜水平，免疫细胞化学， 分光光度，层析，酶学，组织培养， 移植和组织培养允许相关的 形态、生化和生理参数。 主要问题仍然是人类胰岛细胞的障碍 移植。能否开发出有效的方法来解决 人胰岛的分离纯化？方法是否可以 允许胰岛内分泌移植物纯化的研究进展 无需患者即可避免排斥反应 免疫抑制？1型糖尿病的病因会是 在移植的移植物中重新表达，从而损害了它们的 功能呢？如果是这样，综合征的重新表达是否与 宿主与供体-CaN的免疫学相似性 不匹配(同种异体移植)绕过自身免疫 现象。希望这篇文章中概述的实验 提案将提供基础研究，这些研究可能导致 其中一些问题的答案。