Unfathomed Nanomessages to the Heart: Translational Implications of Stem Cell-Derived, Progenitor Cell Exosomes in Cardiac Repair and Regeneration

Charan Thej,Raj Kishore

doi:10.3390/cells10071811

Abstract

Exosomes formed from the endosomal membranes at the lipid microdomains of multivesicular bodies (MVBs) have become crucial structures responsible for cell communication. This paracrine communication system between a myriad of cell types is essential for maintaining homeostasis and influencing various biological functions in immune, vasculogenic, and regenerative cell types in multiple organs in the body, including, but not limited to, cardiac cells and tissues. Characteristically, exosomes are identifiable by common proteins that participate in their biogenesis; however, many different proteins, mRNA, miRNAs, and lipids, have been identified that mediate intercellular communication and elicit multiple functions in other target cells. Although our understanding of exosomes is still limited, the last decade has seen a steep surge in translational studies involving the treatment of cardiovascular diseases with cell-free exosome fractions from cardiomyocytes (CMs), cardiosphere-derived cells (CDCs), endothelial cells (ECs), mesenchymal stromal cells (MSCs), or their combinations. However, most primary cells are difficult to culture in vitro and to generate sufficient exosomes to treat cardiac ischemia or promote cardiac regeneration effectively. Pluripotent stem cells (PSCs) offer the possibility of an unlimited supply of either committed or terminally differentiated cells and their exosomes for treating cardiovascular diseases (CVDs). This review discusses the promising prospects of treating CVDs using exosomes from cardiac progenitor cells (CPCs), endothelial progenitor cells (EPCs), MSCs, and cardiac fibroblasts derived from PSCs.

Highlights

Cardiovascular diseases (CVDs) such as coronary heart disease, heart failure, atherosclerosis, congenital heart disease, arrhythmic disorders, coronary artery disease, and peripheral artery disease are still the primary cause of health burden globally [1]
Transcriptomic analysis of extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs), cardiac progenitor cells (CPCs), and cortical bone stem cells revealed the differential and similar composition of various mRNAs, miRNAs, and other noncoding RNAs [32]
Several studies have demonstrated that serum exosome proteins differ from proteins carried by several cancer cells, and the detection of cancer-specific protein markers could help in reliable cancer diagnosis

Summary

Introduction

Cardiovascular diseases (CVDs) such as coronary heart disease, heart failure, atherosclerosis, congenital heart disease, arrhythmic disorders, coronary artery disease, and peripheral artery disease are still the primary cause of health burden globally [1]. Small RNAs, and growth factors, exosomes are recognized to be critical mediators of cell–cell communication during homeostasis and pathophysiological conditions, the signaling mechanisms of endogenous exosomes in tissue homeostasis remain to be established. Their differential biogenesis is broadly classified as apoptotic bodies, microvesicles/microparticles, and exosomes. The term “exosome” was later coined by Rose Johnstone These studies and many subsequent ones have demonstrated that, unlike other EVs, exosomes originate via the endocytic route due to the inward budding of the limiting membrane of endocytic compartments that fuse and lead to early endosome formation. In the following two sections of this review, we discuss the exosomal cargo of cells in general and specific to the cargo of pluripotent stem cells (PSCs) and cardiac tissue-specific progenitors derived from them

Exosomal Genetic Cargo

Exosomal Proteins and Lipids

Stem Cell Exosomes for Cardiac Repair

Findings

Discussion