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Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
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Extracellular vesicles and their microRNA cargo in ischaemic stroke

Josie L Fullerton1, Caitlin C Cosgrove1, Rebecca A Rooney1

  • 1Institute of Cardiovascular and Medical Sciences College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

The Journal of Physiology
|April 14, 2022
PubMed

Insights

Extracellular vesicle-derived microRNAs (miRNAs) show promise as biomarkers and therapeutics for acute ischemic stroke (AIS). Specific miRNAs, like miRNA-124, are altered in AIS and can be delivered via mesenchymal stem cell EVs for neuroprotection.

Area of Science:

  • Biochemistry and Molecular Biology
  • Neuroscience
  • Regenerative Medicine

Background:

  • Acute ischemic stroke (AIS) is a major cause of death and disability worldwide.
  • MicroRNAs (miRNAs), encapsulated in extracellular vesicles (EVs), are crucial for intercellular communication and show potential as biomarkers and therapeutics.
  • Mesenchymal stem cell (MSC)-derived EVs are recognized for their therapeutic properties and ability to transport miRNAs.

Purpose of the Study:

  • To investigate the role of EV-derived miRNAs as potential biomarkers and therapeutic agents in acute ischemic stroke (AIS).
  • To explore the commonalities in altered miRNAs across preclinical and clinical AIS studies, particularly those involving MSC-derived EVs.
  • To assess the therapeutic potential of specific miRNAs, such as miRNA-124, miRNA-17 family, and miRNA-30 family, in the context of AIS.

Main Methods:

  • Review and synthesis of preclinical and clinical studies on EV-derived miRNAs in AIS.
  • Analysis of specific miRNA alterations (e.g., miRNA-124, miRNA-17 family, miRNA-30d/a) in relation to AIS pathology and MSC-EV treatment.
  • Evaluation of miRNA-124 as both a biomarker and therapeutic agent in experimental stroke models.
  • Investigation of miRNA-17 family alterations in preclinical, clinical, and MSC-EV studies.
  • Assessment of miRNA-30d and -30a for their therapeutic effects and biomarker potential.

Main Results:

  • AIS is associated with specific EV-derived miRNAs, with notable alterations observed in miRNA-124, the miRNA-17 family, and the miRNA-30 family.
  • miRNA-124 functions as both an EV-packaged biomarker and a potential EV-loaded therapeutic in experimental AIS models.
  • Alterations in the miRNA-17 family and miRNA-17-92 cluster are identified across preclinical, clinical, and MSC-EV studies.
  • miRNA-30d and -30a, when overexpressed from MSCs, demonstrate therapeutic effects and are implicated as clinical biomarkers.

Conclusions:

  • EV-derived miRNAs are vital for understanding AIS neuropathology.
  • Circulating EV-packaged miRNAs hold significant clinical value as biomarkers for AIS.
  • Modulating specific EV-derived miRNAs presents a novel therapeutic strategy for AIS treatment, particularly using MSC-derived EVs.
Keywords:
cargoclinicalextracellular vesiclesischaemic strokemicroRNAspreclinical

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