Recent technical advances to study metabolomics of extracellular vesicles

Abstract Extracellular vesicles (EVs) serving as cell-to-cell communication mediators have rapidly attracted attention from researchers for biomarker discovery, diagnostics and therapeutics. EVs participate in multiple physiological processes and can incorporate various biological molecules. The metabolite is an important molecular type carried by EVs, yet the least researched component compared to proteins and RNAs. Metabolomics is used to investigate the downstream metabolic alternations which reflect cell phenotypes and provide unique insights into disease pathogenesis and biological mechanisms. Recently, the interest of the research community in EV metabolomics has been increasing for its promising diagnostic values of various diseases. The knowledge about the composition and function of the EV metabolome is accumulating. But the clinical applications are still limited by the lack of robust and reproducible methods for obtaining high purity EV samples. In this short review, we will summarize the recent technical advances of EV isolation and purification and the downstream analytical methods for the related metabolic analysis. We will also discuss the new techniques that are needed to move this field forward and the future directions of EV metabolomics.