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Review
. 2021 Mar 16;22(6):3023.
doi: 10.3390/ijms22063023.

Extracellular Vesicles from Mesenchymal Stromal Cells for the Treatment of Inflammation-Related Conditions

Sean T Ryan  1 , Elham Hosseini-Beheshti  2 , Dinara Afrose  3 , Xianting Ding  4 , Binbin Xia  5 , Georges E Grau  2 , Christopher B Little  1 , Lana McClements  3 , Jiao Jiao Li  1   5
Affiliations
Review

Extracellular Vesicles from Mesenchymal Stromal Cells for the Treatment of Inflammation-Related Conditions

Sean T Ryan et al. Int J Mol Sci. .

Abstract

Over the past two decades, mesenchymal stromal cells (MSCs) have demonstrated great potential in the treatment of inflammation-related conditions. Numerous early stage clinical trials have suggested that this treatment strategy has potential to lead to significant improvements in clinical outcomes. While promising, there remain substantial regulatory hurdles, safety concerns, and logistical issues that need to be addressed before cell-based treatments can have widespread clinical impact. These drawbacks, along with research aimed at elucidating the mechanisms by which MSCs exert their therapeutic effects, have inspired the development of extracellular vesicles (EVs) as anti-inflammatory therapeutic agents. The use of MSC-derived EVs for treating inflammation-related conditions has shown therapeutic potential in both in vitro and small animal studies. This review will explore the current research landscape pertaining to the use of MSC-derived EVs as anti-inflammatory and pro-regenerative agents in a range of inflammation-related conditions: osteoarthritis, rheumatoid arthritis, Alzheimer's disease, cardiovascular disease, and preeclampsia. Along with this, the mechanisms by which MSC-derived EVs exert their beneficial effects on the damaged or degenerative tissues will be reviewed, giving insight into their therapeutic potential. Challenges and future perspectives on the use of MSC-derived EVs for the treatment of inflammation-related conditions will be discussed.

Keywords: Alzheimer’s disease; cardiovascular disease; extracellular vesicles; inflammation; mesenchymal stromal cells; osteoarthritis; preeclampsia; regeneration; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Extracellular vesicle (EV) biogenesis, secretion, and uptake [56]. Exosomes (20–150 nm) are intraluminal vesicles (ILVs) formed by inward budding of the endosomal membrane during maturation of multivesicular body (MVB), which are secreted upon fusion of the MVBs with the plasma membrane. Microvesicles (50–1000 nm) are a heterogeneous group of vesicles with different membranes depending on their origin and morphology. Apoptotic bodies are shedding vesicles derived from apoptotic cells. After their release into the extracellular space, EVs can bind to cell surface receptors to initiate intracellular signalling pathways. EVs can also be internalised through processes such as macropinocytosis and phagocytosis, or by fusion with the plasma membrane. The cargo of EVs consisting of proteins, nucleic acids and lipids are released in the intracellular space or taken up by the endosomal system of the recipient cell. Reproduced with permission from [56].
Figure 2
Figure 2
Summary of the application of mesenchymal stromal cell (MSC)-derived EVs in treating inflammation-related conditions as covered in this review: osteoarthritis, rheumatoid arthritis, Alzheimer’s disease, cardiovascular disease, and preeclampsia.
See this image and copyright information in PMC

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