Mechanisms and Optimization Strategies of Paracrine Exosomes from Mesenchymal Stem Cells in Ischemic Heart Disease

Abstract

The morbidity and mortality of myocardial infarction (MI) are increasing worldwide. Mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal and differentiation capabilities that are essential in tissue healing and regenerative medicine. However, the low implantation and survival rates of transplanted cells hinder the widespread clinical use of stem cells. Exosomes are naturally occurring nanovesicles that are secreted by cells and promote the repair of cardiac function by transporting noncoding RNA and protein. In recent years, MSC-derived exosomes have been promising cell-free treatment tools for improving cardiac function and reversing cardiac remodeling. This review describes the biological properties and therapeutic potential of exosomes and summarizes some engineering approaches for exosomes optimization to enhance the targeting and therapeutic efficacy of exosomes in MI.

Stem Cell Therapy against Ischemic Heart Disease

“…The observed stem-cell-mediated benefits have been shown to be attributable to the paracrine functions of stem cells. In this aspect, exosomes appear to play a key role, particularly because of their contents of microRNAs, which have been found to be of great clinical potential in the treatment of ischemic heart disease [118,144,[191][192][193]. Taking into account the limited availability of autologous stem cells, exosomes from their allogeneic and xenogeneic counterparts may also offer significant therapeutic advantages [104].…”

Research hotspots and emerging trends of mesenchymal stem cells in cardiovascular diseases: a bibliometric-based visual analysis

“…MSCs promote healing in ischemic tissue-associated diseases through pro-angiogenic secretion of proteins, again in relation to MSC exosomes, making them a promising resource for regenerative medicine and a wide range of in vitro applications (104)(105)(106). In addition, a variety of exosome-derived proteases have been shown to favor cardiomyocyte repair and regeneration through multiple mechanisms (107)(108)(109)(110). For example, ATP deficiency and initiation of apoptosis during ischemia and reperfusion are supported by proteomic defects in enzymes critical for fatty acid oxidation, glycolysis, and the tricarboxylic acid cycle as well as proteomic excesses of pro-apoptotic proteins.…”