Exosomal miRNAs for cardiac repair: a cell-free therapeutic approach

Although cardiovascular diseases represent the major cause of mortality worldwide, cardiac tissue regeneration is still challenging in the clinics. For about 20 years, cell-therapies based on stem cell transplantations have risen interest and enthusiasm for their potential medical application, until entering the clinical trials, where their numerous limitations came out. Recently, alternative promising approaches related to exosomal miRNAs have emerged. Exosomes are vesicles sized 30-150 nm that mediate paracrine signalling, which is the main mechanism responsible for the beneficial effects of stem cells. They act as nanocarriers for miRNAs, short nucleotidic sequences that negatively regulate protein expression in recipient cells through post-transcriptional gene silencing. Nowadays, miRNAs involvement in cardioprotection has been widely corroborated, as they regulate proliferation, growth, apoptosis in cardiomyocytes as well as angiogenesis in endothelial cells and affect inflammatory processes in immune cells. Due to the broad potential of miRNAs and the versatility of exosomes as drug delivery system, here, I am going to discuss exosome-based regenerative therapies, focusing on the modulation of miR-21-5p and miR-212/132, relevant for manifold diseases affecting heart, ranging from recovery after myocardial infarction in heart failure patients, to cardioprotection during anticancer treatments. Furthermore, I will propose the use of exosomes conjugated with peptides able to selectively target the heart as a practical improvement to avoid therapy invasiveness and allow targeted delivery of exosomes even with systemic administrations. To conclude, miRNA-based exosomal therapy stands out as a revolutionary approach to finely modulate almost all endogenous biological processes, potentially allowing the treatment and prevention of many diseases.