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Review
. 2018 May;15(5):4067-4079.
doi: 10.3892/etm.2018.5993. Epub 2018 Mar 22.

Extracellular vesicles in mesenchymal stromal cells: A novel therapeutic strategy for stroke

Affiliations
Review

Extracellular vesicles in mesenchymal stromal cells: A novel therapeutic strategy for stroke

Yingchen Li et al. Exp Ther Med. 2018 May.

Abstract

A stroke is a focal cerebral insult that frequently causes severe neurological deficit and mortality. Recent studies have demonstrated that multipotent mesenchymal stromal cells (MSCs) hold great promise for neurovascular remodeling and neurological function recovery following a stroke. Rather than a direct replacement of parenchymal brain cells, the therapeutic mechanism of MSCs is suggested to be the secretion of soluble factors. Specifically, emerging data described MSCs as being able to release extracellular vesicles (EVs), which contain a variety of cargo including proteins, lipids, DNA and various RNA species. The released EVs can target neurocytes and vascular cells and modify the cell's functions by delivering the cargo, which are considered to mediate the neural restoration effects of MSCs. Therefore, EVs may be developed as a novel cell-free therapy for neurological disorders. In the present review, the current advances regarding the components, functions and therapeutic potential of EVs are summarized and the use of MSC-derived EVs as a promising approach in the treatment of stroke are highlighted.

Keywords: exosomes; extracellular vesicles; mesenchymal stromal cells; microvesicles; stroke.

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Figures

Figure 1.
Figure 1.
Timeline (1969–2016) of articles referring to extracellular vesicles, microvesicles and exosomes in PubMed (https://www.ncbi.nlm.nih.gov/pubmed/).
Figure 2.
Figure 2.
Transmission electron microscopy of human umbilical cord mesenchymal stromal cells. Massive blebbings of the membrane were observed in this image, the microvesicles, MVBs and exosomes are indicated in the dashed squares. (A) Microvesicles: Large (100–1,000 nm), derived from the plasma membrane. (B) MVBs: Contain exosomes. (C) Exosomes: Small (30–120 nm), derive from MVBs. MVBs, multivesicular bodies.
Figure 3.
Figure 3.
Isolation of extracellular vesicles. (A) Ultracentrifugation. (B) Polymeric precipitation. (C) Size exclusions, (D) ATPS. ATPS, aqueous two phase system; DEX, dextran; EDTA, ethylene diamine tetraacetic acid; EQ, ExoQuick; FBS, fetal bovine serum; EVs, extracellular vesicles; PEG, polyethylene glycol; RT, room temperature; SN, supernatant.
Figure 4.
Figure 4.
Biological functions of exosomes and microvesicles. (1) Stimulation of recipient cells by functioning as signal complexes; (2) Transfer of surface receptors or lipids into recipient cells; (3) Delivery of cytoplasmic proteins and nucleic acids via the endocytic pathway; (4) Delivery of cytoplasmic proteins and nucleic acids by membrane fusion. miRNA, micro RNA; MVB, multivesicular body.

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