Abstract
Mesenchymal stem cells (MSCs) are adult stromal cells with the capacity to differentiate into multiple types of cells. MSCs represent an attractive option in regenerative medicine due to their multifaceted abilities for tissue repair, immunosuppression, and anti-inflammation. Recent studies demonstrate that MSCs exert their effects via paracrine activity, which is at least partially mediated by extracellular vesicles (EVs). MSC-derived EVs (MSC-EVs) could mimic the function of parental MSCs by transferring their components such as DNA, proteins/peptides, mRNA, microRNA (miRNA), lipids, and organelles to recipient cells. In this review, we aim to summarize the mechanism and role of miRNA transfer in mediating the effects of MSC-EVs in the models of human diseases. The first three sections of the review discuss the sorting of miRNAs into EVs, uptake of EVs by target cells, and functional transfer of miRNAs via EVs. Then, we describe the composition of miRNAs in MSC-EVs. Next, we provide the existing evidence that MSC-EVs affect the outcomes of renal, liver, heart, and brain diseases by transferring their miRNA contents. In conclusion, EV-mediated miRNA transfer plays an important role in disease-modulating capacity of MSCs.
Highlights
Mesenchymal stem cells (MSCs) are a heterogeneous population of progenitor cells which possess angiogenic, anti-apoptotic, and immunomodulatory properties
Mesenchymal stem (stromal) cells (MSCs)-extracellular vesicles (EVs) are cell-free products and reduce the risks associated with the use of native or engineered MSCs
The effects of MSC-derived EVs (MSC-EVs) are of equal potency to those observed with whole MSCs
Summary
Mesenchymal stem (stromal) cells (MSCs) are a heterogeneous population of progenitor cells which possess angiogenic, anti-apoptotic, and immunomodulatory properties. The initial enthusiasm for MSCs in tissue repair was based on the findings that MSCs are able to home to the damaged tissues and differentiate into many types of cells. EVs are membrane-contained vesicles released by most types of cells including MSCs. A crucial criterion of EVs is that they must be harvested from extracellular fluids such as tissue culture or bodily compartment through ultracentrifugation based on the position statement from the International Society for Extracellular Vesicles (ISEV) [7]. EVs can be broadly classified into three subtypes based upon vesicle sizes and methods of cellular release: exosomes (30–130 nm), microvesicles (100–1000 nm), and apoptotic bodies (50–4000 nm). Exosomes are produced after the fusion of multivesicular bodies (MVB), which are endocytic organelles containing many luminal vesicles, with the plasma membrane. Both microvesicles and apoptotic bodies are formed by direct
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