DEVELOPMENT OF METHODS TO IMPROVE ISOLATED PANCREATIC ISLET FUNCTION

改善离体胰岛功能的方法的开发

• 批准号: 7958773
• 负责人: LUIS Alberto FERNANDEZ
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958773
• 关键词: Apoptosis; Architecture; Area; Clinical Research; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Evaluation; Flow Cytometry; Funding; Glucose; Grant; Human; Hypoxia; Institution; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Link; Measurement; Methodology; Methods; Modeling; Mus; Patients; Physiological; Preparation; Primates; Publications; Quality Indicator; Reporting; Research; Research Personnel; Resources; Services; Source; Streptozocin; Testing; Tissues; Transplantation; United States National Institutes of Health; Wisconsin; Work; cytokine; diabetic; improved; islet; method development; nonhuman primate; novel strategies; pancreatic islet function; response; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To develop new methods for the isolation and evaluation of isolated pancreatic islets for the purpose of transplantation into patients with type I diabetes. The results obtained using non-human primate tissue will assist in the development of methodologies for the isolation and assessment of human islets. Methods include; 1) characterization of the physiological response to glucose as a rapid potency indicator of the quality of the islet preparation prior to transplantation,. 2) determination of the effects of hypoxia on islet viability and function after isolation, 3) determination of the sensitivity of islets to cytokine induced apoptosis. Determination of viability and apoptosis will be performed using a novel approach in which islets can be analyzed intact, preserving their complete architecture using Complex Object Parametric Analyzer and Sorter (COPAS) flow cytometry. We will also evaluate the ability of COPAS viability and apoptosis measurements to provide predictive data on islet function after transplantation using a marginal mass model of human islet transplant in streptozotocin-induced diabetic immuno-deficient mice. In addition, the development of rapid, accurate, and predictive tests of islet viability and function post isolation will contribute to significant improvements in post transplant success. This research used WNPRC Research Services. NOTE: This investigator did not have any projects, funding or publications involving the Primate Center during this reporting period; but he is active with clinical research, funding and publications related to this work; thus, we are including this subproject for an additional year to demonstrate the important link between his recent nonhuman primate work and his current human research in this area. Publications are pending.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：开发新方法，以分离和评估分离的胰岛，以将其移植到I型糖尿病患者中。 使用非人类灵长类动物组织获得的结果将有助于开发人类胰岛分离和评估的方法论。 方法包括； 1）表征对葡萄糖的生理反应，是移植前胰岛制剂质量的快速效力指标。 2）确定缺氧对分离后胰岛活力和功能的影响，3）确定胰岛对细胞因子诱导凋亡的敏感性。 将使用一种新的方法来确定生存力和凋亡的确定，在该方法中可以完整分析胰岛，并使用复杂的对象参数分析仪和分子（COPAS）流式细胞仪保存其完整的体系结构。我们还将评估使用人类胰岛移植的边缘质量模型在链霉菌素诱导的糖尿病免疫缺陷型小鼠中，使用人类胰岛移植的边缘质量模型在移植后提供有关胰岛功能的预测数据的能力。此外，胰岛生存能力和功能后的快速，准确和预测测试的发展将有助于重要 改进移植后成功。这项研究使用了WNPRC研究服务。 注意：在此报告期间，该调查员没有任何涉及灵长类动物中心的项目，资金或出版物；但是他积极从事与这项工作有关的临床研究，资金和出版物；因此，我们将此副本包括在内，以证明他最近的非人类灵长类动物工作与他目前在该领域的人类研究之间的重要联系。 出版物正在等待。