The impact of natural and engineered extracellular vesicles on post-myocardial infarction angiogenesis

Myocardial infarction (MI) causes significant disintegration to the coronary microcirculation. Reperfusion following MI is essential to ensure the viability of cardiac tissue. Angiogenesis after MI involves interactions among various cell types, especially stem cells, which can be exploited as a promising therapeutic approach. Extracellular vesicles (EVs) transfer signaling molecules to adjacent cells in a paracrine manner, thereby playing a vital role in intercellular communication. This review summarizes the angiogenic regulating effects of EVs involved in the MI microenvironment and the therapeutic benefits of exogenous stem cell-derived EVs, and further clarifies the underlying mechanisms. We also discuss advanced methodologies to increase the yield and enhance the biological activities of engineered EVs to address major limitations preventing clinical applications to improve cardiac repair. Finally, highly efficient delivery systems are proposed to improve the efficacy of EVs for treatment of MI.