Lack of cardiac benefit after intramyocardial or intravenous injection of mesenchymal stem cell-derived extracellular vesicles supports the need for optimized cardiac delivery.

Aim: To determine the differences in improvement in cardiac function by intramyocardial (IM) . intravenous (IV) injection of human bone mesenchymal stem cell-derived extracellular vesicles (HBMSC-EV) after acute MI.

Methods: FVB mice underwent acute MI via left anterior descending coronary artery ligation and subsequent injection of: (1) IM saline control; (2) IM HBMSC-EV; (3) IV saline control; and (4) IV HBMSC-EV.