Multimarker surface signatures of human islet derived extracellular vesicles

人胰岛来源的细胞外囊泡的多标记表面特征

• 批准号: 10708816
• 负责人: David Aaron Routenberg
• 金额: $ 70.53万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708816
• 关键词: Affect; Alpha Cell; Autoimmune; Beta Cell; Biological Assay; Biological Markers; Biology; Blood; Cell Culture Techniques; Cell Line; Cell model; Cells; Cellular Stress; Classification; Clinical; Collaborations; Complex; Confidential Information; Detection; Development; Diagnosis; Diagnostic; Disease; Early identification; Environment; Evaluation; Event; Exocrine pancreas; Florida; Functional disorder; Goals; Government; Health; Health Care Costs; Health Status; Human; Human Cell Line; Individual; Industrialization; Inflammation; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Mass Spectrum Analysis; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; Pancreas; Pathologic; Patients; Persons; Phase; Plasma; Population; Proteins; Proteomics; Protocols documentation; Sampling; Slice; Solid; Stress; Subgroup; Surface; Technical Expertise; Techniques; Technology; Tissue Sample; Tissues; United States; Universities; assay development; cell type; clinically relevant; cohort; combinatorial; disorder risk; extracellular vesicles; immune modulating agents; improved; induced pluripotent stem cell; islet; liquid biopsy; minimally invasive; molecular marker; new technology; novel; peripheral blood; prevent; prognostic; protein biomarkers; protocol development; response; screening; success; technology validation

We propose an industrial-academic collaboration in response to RFA-DK-21-016 titled “Characterization of Islet- derived Extracellular Vesicles for Improved Detection, Monitoring, Classification, and Treatment of Type 1 Diabetes”. The objectives are to identify combinations of surface markers that define populations of EV originating from the major cells of the islets of Langerhans and exocrine pancreatic tissue and to apply novel technologies for isolating and deeply characterizing these unique EV populations. We will build upon recent successes at MSD in developing a novel technique for EV surface marker screening and a multimarker immunoaffinity technique for isolating highly specific EV populations. These techniques will be adapted to the specific EV populations of the pancreas, which will enable us to observe changes to the EV repertoire related to pathological events and to identify populations of EVs or specific EV cargo that may serve as a remote biomarker for islet related events. We will apply our expertise in ultrasensitive ECL-based assays to develop assays that enable detection of these pancreas-specific EVs from peripheral blood. This proposal combines the technical expertise of Meso Scale Diagnostics, LLC., with expertise in the biology of islet-derived extracellular vesicles of our collaborator, Dr. Edward Phelps at the University of Florida.

针对RFA-DK-21-016号文件，我们提出了产业界和学术界的合作方案，标题为： 衍生的细胞外小泡用于改进1型患者的检测、监测、分类和治疗 糖尿病“。目标是确定定义电动汽车种群的表面标记的组合 来源于朗格汉斯胰岛和胰腺外分泌组织的主要细胞及其应用 用于分离和深入描述这些独特的电动汽车种群的技术。我们将在最近的基础上 MSD在开发EV表面标记筛选和多标记新技术方面取得成功 免疫亲和技术用于分离高特异性EV种群。这些技术将适用于 胰腺的特定EV种群，这将使我们能够观察与以下相关的EV谱系的变化 病理事件并识别可能作为远程生物标志物的EV群体或特定EV货物 用于与小岛相关的活动。我们将应用我们在基于ECL的超灵敏分析方面的专业知识来开发 能够从外周血中检测到这些胰腺特异的EV。这项建议结合了技术上的 中尺度诊断公司的专业知识，在胰岛细胞外小泡生物学方面的专业知识 我们的合作者，佛罗里达大学的爱德华·菲尔普斯博士。