Multifaceted mechanisms and targeted delivery of mesenchymal stem cell-derived exosomes in cardiovascular diseases: a translational medicine perspective

As cardiovascular disease (CVD) is the leading cause of death worldwide, its prevention and treatment is urgent and new therapeutic targets are urgently needed. Mesenchymal stem cell-derived exosomes (MSC-Exo) have emerged as promising nanotherapeutics due to their regenerative capacity, low immunogenicity, and multilineage differentiation potential. This review systematically integrates the therapeutic mechanisms of MSC-Exo in seven major cardiovascular indications, including myocardial infarction, myocardial ischemia-reperfusion injury, atherosclerosis, heart failure, cardiomyopathy, myocarditis, and pulmonary hypertension, while exploring advanced engineering strategies to enhance its efficacy. Through comprehensive analysis of current preclinical studies, we demonstrated that MSC-Exo mainly exerts cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, fibrosis, inhibiting inflammatory responses, and regulating immune responses. In addition, we also highlight innovative delivery methods, including intrapericardial administration for immunomodulation, ischemic myocardium-targeting peptides, and functional hydrogel encapsulation that significantly improve exosome retention and bioavailability. The fusion of biological mechanisms and engineering solutions makes MSC-Exo a multifunctional platform for cardiovascular regenerative medicine, with emerging clinical translation potential through optimized delivery systems and precise targeting strategies, in order to provide new ideas for the treatment of cardiovascular diseases with MSC-Exo.