Mitochondrial Transfer through Pericardium Contributes to Functional Recovery in Ischemic Cardiomyopathy

<jats:title>Abstract</jats:title> <jats:p>Although mesenchymal stem cell transplantation has been efficacious in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy.<jats:bold> </jats:bold>Mitochondrial transfer was examined in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes under hypoxic conditions. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation.<jats:bold> </jats:bold><jats:italic>In vitro</jats:italic>, we observed mitochondrial transfer, which required formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cexhibited mitochondrial transfer three days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. In conclusion, mitochondrial transfer is vital for successful cell transplantation therapies and promotes improved treatment outcomes in ischemic cardiomyopathy.</jats:p>