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.

我们提出了一个工业-学术合作，以响应RFA-DK-21-016题为“表征胰岛- 衍生的细胞外囊泡用于改进1型糖尿病的检测、监测、分类和治疗 糖尿病”。目的是确定界定EV群体的表面标志物的组合 来源于胰岛和外分泌胰腺组织的主要细胞，并应用新的 用于隔离和深入表征这些独特电动汽车群体的技术。我们将建立在最近 MSD在开发EV表面标记筛选新技术和多标记 免疫亲和技术用于分离高度特异性EV群体。这些技术将适用于 胰腺的特定EV群体，这将使我们能够观察与以下相关的EV库的变化： 病理事件，并鉴定可用作远程生物标志物的EV群体或特定EV货物 与胰岛相关的事件。我们将运用我们在超灵敏ECL检测方面的专业知识，开发出 能够从外周血中检测这些胰腺特异性EV。该提案结合了技术 Meso Scale Diagnostics，LLC.的专业知识，具有胰岛衍生细胞外囊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。