Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Abstract

When injected into acutely infarcted rodent or pig hearts, naturally secreted nanovesicles known as exosomes from cardiac-derived progenitor cells (CPCs) reduce scar size and improve cardiac function. In this regard, exosomes fully mimic the benefits of injecting their parent cells. This recognition paves the way to the development of exosome-based, cell-free treatments for heart disease that could possibly supplant cellbased therapies. Mechanisms of benefit of these vesicles are incompletely understood but cytoprotection, stimulation of angiogenesis, induction of antifibrotic cardiac fibroblasts, and modulation of M1/M2 polarization of macrophages infiltrating the infarcted region can all play important roles. Accordingly, the beneficial molecules carried by CPC-secreted exosomes have been identified only in part but cytoprotective and proangiogenic microRNAs (miRNA) and proteins have been described. Besides CPC-secreted exosomes, vesicles released from other cell types including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iSPCs) have also been associated with cardioprotection. This review aims to discuss recent advances in our understanding of the role of secreted vesicles in cardiac repair, with a focus on CPC-derived exosomes.

Exosomes derived from pro‐inflammatory bone marrow‐derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization

“…11,43 The mechanisms of cardioprotection of BMSC-derived exosomes have not been fully elucidated, while the effects of anti-inflammation, immunoregulation, angiogenesis and the modulation of M1/M2 macrophage polarization have gradually attracted scholars' attention. 44 Macrophages are involved in heart injury and repair after MI and F I G U R E 5 The effects of L-Exo on inflammation and phenotype of rat peritoneal macrophages under LPS treatment. Firstly, rat peritoneal macrophages were pre-cultured with Exo and L-Exo at dose of 10 μg/mL for 24 h and then followed by treatment with LPS (500 ng/mL) for 24 h. A, The characteristic morphology of rat peritoneal macrophages co-cultured with Exo and L-Exo under LPS stimulation was shown (200×).…”

The pulmonary microvasculature entraps induced vascular progenitor cells (iVPCs) systemically delivered after cardiac ischemia‐reperfusion injury: Indication for preservation of heart function via paracrine effects beyond engraftment

“…These released factors can either protect the heart tissue directly or stimulate progenitor cells and thus promote cardiac repair indirectly. There is a growing body of evidence that exosomes secreted by various cell types have significant beneficial effects after myocardial I/R injury . Further research is required to prove the entrapped targ‐iVPCs are indeed able to release Tand‐scFv Sca‐1+GPIIb/IIIa‐ coated exosomes and home to the ischemic myocardium.…”

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

“…It is noteworthy to mention that in some cases, depending on cell-type as well as genotypic and functional status of the cells, specific components in the exosomes may not be beneficial but rather, harmful to the cardiovascular system (Barile et al, 2017a). For example, the progression of heart failure may alter the miRNA cargos in cardiac-derived exosomes and suppress their regenerative activities (Qiao et al, 2019).…”