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

基本信息

批准号：
10518967
负责人：
David Aaron Routenberg
金额：
$ 71.82万
依托单位：
MESO SCALE DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
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/10518967
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 Immunomodulators Individual Industrialization Inflammation Insulin-Dependent Diabetes Mellitus Islet Cell Islets of Langerhans Langerhans cell Mass Spectrum Analysis Measures Methods Modeling Monitor Morbidity - disease rate Pancreas Pathologic Patients Persons Pharmacotherapy 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 base cell type clinically relevant cohort combinatorial disorder risk extracellular vesicles 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

项目摘要

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.

我们提出了一种工业学术合作，以回应RFA-DK-21-016，标题为“胰岛的特征 - 衍生的细胞外囊泡可改善1型的检测，监测，分类和治疗糖尿病”。目标是确定定义EV种群的表面标记的组合起源于Langerhans和外分泌胰腺组织的主要细胞，并应用新型用于隔离和深入表征这些独特的EV种群的技术。我们将基于最近 MSD在开发一种用于EV表面标记筛选和多标记的新技术方面取得了成功用于隔离高度特异性EV种群的免疫亲和力技术。这些技术将适应胰腺的特定电动汽车群体，这将使我们能够观察到与EV曲目的更改病理事件并确定可以用作远程生物标志物的电动汽车或特定EV货物的种群对于胰岛相关事件。我们将在基于超敏的ECL测定中应用我们的专业知识，以开发测定法从外周血中启用这些胰腺特异性电动汽车。该建议结合了技术 Meso Scale Diagnostics，LLC。的专业知识，具有胰岛衍生的细胞外蔬菜生物学专业知识我们的合作者，佛罗里达大学的爱德华·菲尔普斯（Edward Phelps）博士。