Extracellular vesicles and their microRNA cargo in ischaemic stroke.

Acute ischaemic stroke (AIS) is a leading cause of death and disability. MicroRNAs (miRNAs) are short non-coding RNAs which hold the potential to act as a novel biomarker in AIS. The majority of circulating miRNAs are actively encapsulated by extracellular vesicles (EVs) produced by many cells and organs endogenously. EVs released by mesenchymal stem cells (MSCs) have been extensively studied for their therapeutic potential. In health and disease, EVs are vital for intercellular communication, as the cargo within EVs can be exchanged between neighbouring cells or transported to distant sites. It is clear here from both current preclinical and clinical studies that AIS is associated with specific EV-derived miRNAs, including those transported via MSC-derived EVs. In addition, current studies provide evidence to show that modulating levels of specific EV-derived miRNAs in AIS provides a novel therapeutic potential of miRNAs in the treatment of stroke. Commonalities exist in altered miRNAs across preclinical and clinical studies. Of those EV-packaged miRNAs, miRNA-124 was described both as an EV-packaged biomarker and as a potential EV-loaded therapeutic in experimental models. Alterations of miRNA-17 family and miRNA-17-92 cluster were identified in preclinical, clinical and MSC-EV-mediated neuroprotection in experimental stroke. Finally, miRNA-30d and -30a were found to mediate therapeutic effect when overexpressed from MSC and implicated as a biomarker clinically. Combined, EV-derived miRNAs will further our understanding of the neuropathological processes triggered by AIS. In addition, this work will help determine the true clinical value of circulating EV-packaged miRNAs as biomarkers of AIS or as novel therapeutics in this setting.