Multimarker surface signatures of human islet derived extracellular vesicles

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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.