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Review
. 2021 Sep 24:15:744840.
doi: 10.3389/fnins.2021.744840. eCollection 2021.

The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury

Teena K J B Gamage  1 , Mhoyra Fraser  1
Affiliations
Review

The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury

Teena K J B Gamage et al. Front Neurosci. .

Abstract

This comprehensive review focuses on our current understanding of the proposed physiological and pathological functions of extracellular vesicles (EVs) in the developing brain. Furthermore, since EVs have attracted great interest as potential novel cell-free therapeutics, we discuss advances in the knowledge of stem cell- and astrocyte-derived EVs in relation to their potential for protection and repair following perinatal brain injury. This review identified 13 peer-reviewed studies evaluating the efficacy of EVs in animal models of perinatal brain injury; 12/13 utilized mesenchymal stem cell-derived EVs (MSC-EVs) and 1/13 utilized astrocyte-derived EVs. Animal model, method of EV isolation and size, route, timing, and dose administered varied between studies. Notwithstanding, EV treatment either improved and/or preserved perinatal brain structures both macroscopically and microscopically. Additionally, EV treatment modulated inflammatory responses and improved brain function. Collectively this suggests EVs can ameliorate, or repair damage associated with perinatal brain injury. These findings warrant further investigation to identify the optimal cell numbers, source, and dosage regimens of EVs, including long-term effects on functional outcomes.

Keywords: biomarkers; exosomes; extracellular vesicles; in-vivo animal models; perinatal brain injury; therapeutic strategies; white matter injury.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram summarizing the role of EVs in the healthy and injured brain. Created with BioRender.com.
FIGURE 2
FIGURE 2
Flow diagram showing the methodical identification and selection of studies investigating the therapeutic potential of EVs to in-vivo models of perinatal brain injury.
FIGURE 3
FIGURE 3
Schematic diagram summarizing methodologies utilized in publications identified by this unbiased review of literature. (A) Highlights studies that utilized bone marrow-derived MSCs. (B) Highlights studies that utilized umbilical cord∗, umbilical cord blood∗ or umbilical cord Wharton’s jelly derived MSCs. (C) Highlights study which utilized rat cortical-derived astrocytes.
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