Abstract
Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell–cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial infarction (MI), partially outperforming cell therapy. EVs may present several desirable features, such as no tumorigenicity, low immunogenic potential, high stability, and fine cardiac reparative efficacy. Furthermore, the natural origin of EVs makes them exceptional vehicles for drug delivery. EVs may overcome many of the limitations associated with current drug delivery systems (DDS), as they can travel long distances in body fluids, cross biological barriers, and deliver their cargo to recipient cells, among others. Here, we provide an overview of the most recent discoveries regarding the therapeutic potential of EVs for addressing cardiac damage after MI. In addition, we review the use of bioengineered EVs for targeted cardiac delivery and present some recent advances for exploiting EVs as DDS. Finally, we also discuss some of the most crucial aspects that should be addressed before a widespread translation to the clinical arena.
Highlights
Cardiovascular diseases (CVDs) include a wide diversity of pathologies of the heart and blood vessels such as coronary artery disease, rheumatic heart disease, cerebrovascular disease, ischemic heart disease, and heart failure [1]
Extracellular vesicles (EVs)’ purity should be tested by the use of multiple complementary methods: (i) western blotting to analyze EVs markers (e.g., CD63, Alix, etc.) and co-isolated contaminants [10]; (ii) nanoparticle tracking analysis (NTA), which can determine particle size and concentration [57]; (iii) conventional transmission electron microscopy (TEM) and the more strongly recommended cryo-TEM [58], or (iv) nanoflow cytometry, that enables the determination of cell surface antigens, the quantification of EV subpopulations based on parental cell markers [59,60], and the lipid nature of the studied particles with cellpermeant, non-fluorescent pro-dyes [61]
EVs are becoming a promising approach in cardiac regenerative medicine
Summary
Cardiovascular diseases (CVDs) include a wide diversity of pathologies of the heart and blood vessels such as coronary artery disease, rheumatic heart disease, cerebrovascular disease, ischemic heart disease, and heart failure [1]. In the context of cell therapy for cardiac repair, EVs show potential advantages over cells, such as the absence of tumorigenicity, lower immunogenic potential, product stability, non-limiting dosage by microvascular plugging or loss of transplanted cell viability, and the existence of multiple approaches to enhance efficacy, including genetic engineering of the parent cells [7,12] For this reason, EVs purified from defined cell types have been investigated as novel therapeutic options for various cardiac diseases including ischemic heart disease and heart failure, as well as for pathogen vaccination, immune-modulatory and regenerative therapies, and drug delivery [16]. We summarize the most relevant studies published in the last five years related to the potential loading mechanisms, surface modification/engineering to target specific cardiac cells, and the use of EVs as new DDS for MI, discussing the challenges and the perspectives of this nascent field
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