A Novel, Cell-Free Therapy to Enter Our Hearts: The Potential Role of Small EVs in Prevention and Treatment of CVD

Abstract

Heart disease constitutes one of the leading causes of morbidity and mortality worldwide. Current therapeutic techniques, such as interventional revascularization, although lifesaving, come along with myocardial injury related to the reperfusion itself, called ischemia-reperfusion injury, which is an added factor for increased morbidity. For that reason, there is an imperative need for novel therapies to be developed that would either prevent or treat myocardial injury. Extracellular vesicles (EVs), specifically small EVs (sEVs), have proven to be important mediators of intercellular communication. The fact that they carry information reflecting that of the parental cell makes them an ideal candidate for diagnostic purposes. sEVs derived from immunoregulatory cells, such as mesenchymal stem cells or cardiac progenitor cells, could also be used therapeutically to exert the primary immunomodulatory function but without carrying the side effects related to cell therapy. Furthermore, as a natural product, they have the added advantage of low immunogenicity, offering the potential for safe drug delivery. In the field of cardiology, there has been great interest in the therapeutic and diagnostic potential of sEVs with significant translational potential. Here, we review the potential use of sEVs in the context of myocardial ischemia and ischemia-reperfusion injury.

Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media

“…They play an essential role in intercellular communication by transferring their compositions, proteins, miRNA, and lipids, to adjacent cells [5]. Moreover, MSC-derived EVs have been specifically studied as regenerative medicine for diseases such as wound healing [6], cardiac disease [7], neurodegeneration, [8,9] liver fibrosis, [10] osteoarthritis [11], and renal failure [12] as an alternative to cell-based therapeutics [13]. Furthermore, EVs can be used for sepsis treatment induced by numerous factors including bacterial infections and COVID-19 [14].…”

Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases

“…EVs allow for easier quality control and better biosecurity. Therefore, MSC‐derived EVs are becoming a new therapeutic approach for treating CVDs 200 . Moreover, increasing evidence shows that EVs derived from ESCs or iPSCs have a promising application prospect in treating CVDs.…”

Cell-Based and Selected Cell-Free Therapies for Myocardial Infarction: How Do They Compare to the Current Treatment Options?

“…These membrane-bound nanovesicles carry a cocktail of critical biological molecules, such as lipids, genetic material (mRNAs, non-coding (nc) RNAs (e.g., miRNAs), and rarely DNAs), cytoskeletal proteins, heat shock proteins, growth factors, cytokines, antigen-presenting molecules, metabolic enzymes, tetraspanins, and other signalling receptors. Several recent studies suggest that their unique cargo composition could make them a novel cell-free tool for disease diagnostics and therapy, including MI [ 159 , 160 ].…”