The Role of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Myocardial Protection: a Review of Current Advances and Future Perspectives

Abstract

Small extracellular vesicles (SEVs) secreted by mesenchymal stromal cells (MSCs) are considered one of the most promising biological therapies in recent years. The protective effect of MSCs-derived SEVs on myocardium is mainly related to their ability to deliver cargo, anti-inflammatory properties, promotion of angiogenesis, immunoregulation, and other factors. Herein, this review focuses on the biological properties, isolation methods, and functions of SEVs. Then, the roles and potential mechanisms of SEVs and engineered SEVs in myocardial protection are summarized. Finally, the current situation of clinical research on SEVs, the difficulties encountered, and the future fore-ground of SEVs are discussed. In conclusion, although there are some technical difficulties and conceptual contradictions in the research of SEVs, the unique biological functions of SEVs provide a new direction for the development of regenerative medicine. Further exploration is warranted to establish a solid experimental and theoretical basis for future clinical application of SEVs.

Keywords: Cardiovascular disease; Exosomes; Mesenchymal stomal cells; Small extracellular vesicles; miRNA.

Fig. 1

Biological characteristics of SEVs. In MSCs, the invaginated cell membrane forms vesicles, and then a variety of proteins, nucleic acids, lipids, and other substances are absorbed by the vesicles to form early endosomes and then MVBs have two pathways: one is to secrete to the extracellular space and release SEVs; another pathway is intracellular lysosomal binding degradation. There are three main ways for cardiomyocytes to absorb SEVs: membrane fusion directly, membrane endocytosis, and receptor binding on the cardiomyocyte membrane. SEVs have a double-membrane structure and are rich in DNA, miRNA, mRNA, polypeptides, enzymes, and other biological active substances. The membrane of SEVs contains tetraspanins, fusion proteins, integrins, etc.