High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia  

作　　者：Andrew M.Larey Thomas M.Spoerer Kanupriya R.Daga Maria G.Morfin Hannah M.Hynds Jana Carpenter Kelly M.Hines Ross A.Marklein 

机构地区：[1]School of Chemical,Materials,and Biomedical Engineering,University of Georgia,Athens,GA,USA [2]Regenerative Bioscience Center,University of Georgia,Athens,GA,USA [3]Department of Chemistry,University of Georgia,Athens,GA,USA

出　　处：《Bioactive Materials》2024年第7期153-171,共19页生物活性材料（英文）

基　　金：supported by the National Science Foundation under BIO-2036968,cooperative agreement EEC-1648035 (RAM),and UGA Research Foundation startup funds (KMH);supported in part by the Glycosciences Training Grant Program (NIH T32 GM145467)。

摘　　要：Due to their immunomodulatory function,mesenchymal stromal cells(MSCs)are a promising therapeutic with the potential to treat neuroinflammation associated with neurodegenerative diseases.This function is mediated by secreted extracellular vesicles(MSC-EVs).Despite established safety,MSC clinical translation has been unsuccessful due to inconsistent clinical outcomes resulting from functional heterogeneity.Current approaches to mitigate functional heterogeneity include‘priming’MSCs with inflammatory signals to enhance function.However,comprehensive evaluation of priming and its effects on MSC-EV function has not been performed.Furthermore,clinical translation of MSC-EV therapies requires significant manufacturing scale-up,yet few studies have investigated the effects of priming in bioreactors.As MSC morphology has been shown to predict their immunomodulatory function,we screened MSC morphological response to an array of priming signals and evaluated MSC-EV identity and potency in response to priming in flasks and bioreactors.We identified unique priming conditions corresponding to distinct morphologies.These conditions demonstrated a range of MSC-EV preparation quality and lipidome,allowing us to discover a novel MSC-EV manufacturing condition,as well as gain insight into potential mechanisms of MSC-EV microglia modulation.Our novel screening approach and application of priming to MSC-EV bioreactor manufacturing informs refinement of larger-scale manufacturing and enhancement of MSC-EV function.

关 键 词：Mesenchymal stromal cell High throughput screening Extracellular vesicle BIOREACTOR MICROGLIA LIPIDOMICS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]