Exosomes in Myocardial Repair: Advances and Challenges in the Development of Next-Generation Therapeutics

Abstract

Myocardial disease is a leading cause of morbidity and mortality worldwide. Given the limited regenerative capacity of the human heart following myocardial injury, stem cell-based therapies have emerged as a promising approach for improving cardiac repair and function. The discovery of extracellular vesicles including exosomes as a key component of the beneficial function of stem cells has generated hope for their use to advance cell-based regenerative therapies for cardiac repair. Exosomes secreted from stem cells are membranous bionanovesicles, naturally loaded with various proteins, lipids, and nucleic acids. They have been found to have anti-apoptotic, anti-fibrotic, as well as pro-angiogenic effects, all of which are crucial to restore function of the damaged myocardium. In this brief review, we will focus on the latest research and debates on cardiac repair and regenerative potential of exosomes from a variety of sources such as cardiac and non-cardiac stem and progenitor cells, somatic cells, and body fluids. We will also highlight important barriers involved in translating these findings into developing clinically suitable exosome-based therapies.

Keywords: exosomes; extracellular vesicles; heart repair; stem cells; therapeutics.

Figure 1

A Scheme Depicting the Discussed Biological Sources of Exosomes for Cardiac Repair, along with Different Strategies for Donor Cell Phenotype Modification AAV, adeno-associated virus; CDC, cardiosphere-derived cell; CSC, cardiac stem cell; EPC, endothelial progenitor cell; ESC, embryonic stem cell; Exo, exosome; iPSC, induced pluripotent stem cell; MSC, mesenchymal stem cell.

Figure 2

Flowchart of GMP-Compliant Production of Exosomes for Clinical Application for Heart Repair GMP, good manufacturing practice; HPLC, high-performance liquid chromatography; QC, quality control; TFF, tangential flow filtration.