IN VITRO METHODS FOR ISLET ISOLATION AND TRANSPLANTATION

胰岛分离和移植的体外方法

• 批准号: 3230658
• 负责人: ORION D HEGRE
• 金额: $ 15.97万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230658
• 关键词: chromatography; collagenase; growth media; histocompatibility antigens; homologous transplantation; human tissue; immunochemistry; infant animal; pancreatic islet transplantation; polyamines; radioimmunoassay; radiotracer; scintillation spectrometry; serum; tissue /cell culture; tissue /cell preparation; tissue /organ preservation; tissue donors; xenotransplantation

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 within the proposal are directed toward the investigation of developing alternate methods for the acquisition of islet tissue. In addition, experiments involve the investigation of a unique method for the production of non-immunogenic islets which can be transplanted without immunosuppression between animals disparate at the major histocompatibility locus. Further understanding of the mechanism by which altered immunogenicity is attained is pursued. Methods for selective cell culture in which cells necessary for immune recognition can be controlled in vitro, are being explored. An experimental model of Type 1 diabetes as well as chemical forms of Type 1 diabetes are being 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. Technicques of immunoassay, morphometric analysis at the ultrastructural and light microscopical level, immunocytochemistry, spectrophotometry, chromatography, enzymology, tissue culture, transplantation 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, compromising their function? It is hoped that experiments in this proposal will provide basic research which may lead to the answers to some of these questions.

这项建议是我们在胰岛领域研究的继续 细胞培养和移植。 这项工作旨在作为一个基础， 对于胰岛细胞移植在1型糖尿病中的最终应用， 糖尿病 建议中的实验是针对 开发用于获取胰岛的替代方法的研究 组织. 此外，实验还涉及对一种独特的 生产非免疫原性胰岛的方法， 在没有免疫抑制的情况下， 主要组织相容性位点 通过以下方式进一步了解该机制： 寻求获得哪种改变的免疫原性。 选择性方法 细胞培养，其中免疫识别所必需的细胞可以 在体外控制，正在探索中。 类型1的实验模型 糖尿病以及1型糖尿病的化学形式正在进行检查， 评估在扭转这些趋势中开发的技术的效用。 高血糖-胰岛素缺乏综合征。 该方法集中于形态数据的采集， 生物化学和生理学研究。 免疫分析技术， 在超微结构和光学显微镜水平上的形态测定分析， 免疫细胞化学，分光光度法，色谱法，酶学，组织 培养，移植允许形态学的相关性， 生化和生理参数。 主要问题仍然是人类胰岛细胞移植的障碍。 能否开发出有效的方法来分离和纯化 人类的小岛 能否开发出纯化 胰岛内分泌移植物避免排斥反应，无需患者 免疫抑制？ 1型糖尿病的病因是否会在 移植的移植物，损害它们的功能？ 人们希望 这项提案中的实验将提供基础研究， 这些问题的答案