Cardiac cells and mesenchymal stem cells derived extracellular vesicles: a potential therapeutic strategy for myocardial infarction

Abstract

Despite improvements in clinical outcomes of acute myocardial infarction (AMI), mortality rates remain high, indicating the need for further understanding of the pathogenesis and developing more effective cardiac protection strategies. Extracellular vesicles (EVs) carry proteins and noncoding RNAs (ncRNAs) derived from different cardiac cell populations, mainly including cardiomyocytes, endothelial cells, endothelial progenitor cells, cardiac progenitor cells, cardiosphere-derived cells, immune cells, fibroblasts and cardiac telocytes have vital roles under both physiological and pathological process such as myocardial infarction (MI). The content of EVs can also indicate the status of their parental cells and serve as a biomarker for monitoring the risk of cardiac injury. Examining these vesicles can offer fresh perspectives on the development of MI and assist in creating innovative treatments. Additionally, mesenchymal stem cells (MSCs) (MSC-EVs) derived EVs have been shown to have significant potential in cardiac regeneration. In this review, we will discuss the current understanding of the role of EVs in cardiac communication, with a focus on the perspectives of EVs from various cardiac cells and MSCs for their potential uses as cardiac therapies after MI.

Keywords: cardiac cells; cell-cell communication; extracellular vesicles; mesenchymal stem cells; myocardial infarction.

Figure 1

Biogenesis, composition and uptake of EVs. cells secrete EVs (including exosomes, ectosomes, and apoptotic bodies) and NVEPs (such as supermeres and exomeres) into the extracellular environment. Exosomes are produced via exocytosis, while ectosomes (such as microvesicles and large oncosomes) are formed through budding. Apoptotic bodies are vesicles formed during apoptosis. EVs contain proteins, DNA, RNA, lipids, metabolites, and mitochondria. EVs can also form a corona on their surface. The membrane of EVs predominantly includes GTPase, MHC class I and II molecules, tetraspanins like CD9, CD63, and CD81, as well as various receptors and ligands. EVs are primarily internalized by target cells via receptor-ligand interactions, clathrin-mediated and clathrin-independent endocytosis, pinocytosis, and direct membrane fusion.

Figure 2

The EV-mediated cross-talk among various cardiac cells such as CMs, ECs, EPCs, CPCs, CDCs, Mϕ, CFs, CTCs and EPDCs under normal, H2O2, hypoxia or ischemia condition, which are involved in the regulation of angiogenesis, inflammatory response, cell death and myocardial fibrosis.

Figure 3

Applications of MSC-EVs in MI. MSC-EVs can be utilized in their original state and enhanced autophagy through preconditioning, gene engineering,membrane modification, encapsulation, hybridization and biomaterial-assisting. EVs can be applied via IM, IV, IC and iPC injection in MI or I/R animal models. MSC-EVs can improve angiogenesis, inflammation, cell death (such as apoptosis, autophgy, pyroptosis, ferroptosis), oxidatve stress and cardiac fibrosis after MI.