The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction

Abstract

Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molecular and cellular basis are urgently needed. Exosomes are a type of extracellular vesicles which contain a large amount of biologically active substances, like lipids, nucleic acids, proteins and so on. Emerging evidence suggests key roles of exosomes in immune regulation post AMI. A variety of immune cells participate in the immunomodulation after AMI, working together to clean up necrotic tissue and repair damaged myocardium. Stem cell therapy for myocardial infarction has long been a research hotspot during the last two decades and exosomes secreted by stem cells are important active substances and have similar therapeutic effects of immunomodulation, anti-apoptosis, anti-fibrotic and angiogenesis to those of stem cells themselves. Therefore, in this review, we focus on the characteristics and roles of exosomes produced by both of endogenous immune cells and exogenous stem cells in myocardial repair through immunomodulation after AMI.

Keywords: Myocardial infarction; exosome; immune cells; immunomodulation; stem cells.

Figure 1

Biogenesis of exosomes. Early endosomes are generated by endocytosis of parent cell. It will then undergo the second invagination of the plasma membrane, thus forming ILVs, and the endosomes that enclose the ILVs are MVBs. MVBs can fuse with the plasma membrane and release the ILVs, namely exosomes. Adapted with permission from , Copyright (2019).

Figure 2

Temporal two different phases of inflammatory process after AMI. In inflammatory phase, neutrophils, M1 macrophages and mast cells dominated, accompanied with damaged cells and tissue digestion. During the following reparative phase, macrophages polarized towards anti-inflammatory type, and dendritic cells as well as regulatory T cells both participated in the resolution of inflammation.

Figure 3

Intercellular communication of immune cells and cardiac inherent cells via exosomes and its contents. In response to AMI, distinct immune cells infiltrated within the infarcted myocardium. Exosomes, with various derivation and different contents, played different roles in inflammation response.