The Promise of Exosomes in Cardiac Repair: When 'Best Things Come in Small Packages'

Myocardial ischaemia continues to be a predominant global cause of mortality, leaving survivors with compromised quality of life and significant loss of functional cardiomyocytes. The main therapeutic approach, which attempts to restore heart function, generally involves myocardial reperfusion. However, this intervention is frequently complicated by the occurrence of myocardial reperfusion injury, which undermines its therapeutic benefits. Consequently, there is an increasing focus on alternative regenerative approaches, such as stem and progenitor cell therapies. Since their initial and successful use in oncology, stem cells have emerged as promising tools for mitigating various pathological conditions. Nonetheless, their efficacy in post-ischaemic myocardial environments is questioned due to their rapid degradation following delivery. Interestingly, small extracellular vesicles, particularly exosomes secreted by stem cells, demonstrate reparative properties akin to those of the stem cells themselves. Indeed, evidence strongly shows that exosomes derived from mesenchymal stem cells, cardiac progenitor cells, and induced pluripotent stem cells exert anti-apoptotic and pro-angiogenic effects in post-ischaemic cardiomyocytes while concomitantly offering protection against myocardial reperfusion injury. In this review, we critically appraise the pivotal findings supporting the potential clinical application of stem cell-derived exosomes, and underscore key considerations necessary to optimise their therapeutic efficacy.