Extracellular vesicles and their microRNA cargo in ischaemic stroke

Fullerton, J. L. , Cosgrove, C. C., Rooney, R. A. and Work, L. (2022) Extracellular vesicles and their microRNA cargo in ischaemic stroke. Journal of Physiology, (doi: 10.1113/JP282050) (PMID:35421904) (Early Online Publication)

[img] Text
267318.pdf - Published Version
Available under License Creative Commons Attribution.

[img] Text (Figure 1)
267318Suppl.pdf - Supplemental Material



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 in altered miRNAs across preclinical and clinical studies exist. 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 in 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.

Item Type:Articles
Additional Information:This work was supported by the Chief Scientific Office Project grant TCS/18/13 (L.M.W.) and the British Heart Foundation (BHF) 4 Year PhD Studentship Awards FS/18/58/34179 (R.R.) and FS/4yPhD/F/21/34158 (C.C.).
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Work, Dr Lorraine and Fullerton, Dr Josie
Authors: Fullerton, J. L., Cosgrove, C. C., Rooney, R. A., and Work, L.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Physiology
ISSN (Online):1469-7793
Published Online:14 April 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Journal of Physiology 2022
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303006Extracellular vesicle mediated microRNA delivery as a therapeutic for ischaemic strokeLorraine WorkOffice of the Chief Scientific Adviser (CSO)TCS/18/13CAMS - Cardiovascular Science
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science
314297BHF 4Yr PhD Studentship Award 2021Rhian TouyzBritish Heart Foundation (BHF)FS/4yPhD/F/21/34158CAMS - Cardiovascular Science