Intravenous mesenchymal stem cell-derived exosomes ameliorate myocardial inflammation in the dilated cardiomyopathy

Mesenchymal stem cells (MSCs) have been shown to be efficacy to attenuating cardiovascular inflammation; however, there are many limitations to stem cell treatment. Present study was to prove MSC derived exosomes (MSC-Exos) could alleviating inflammatory cardiomyopathy by improving the inflammatory microenvironment of myocardium, especially by regulating the activity of macrophages. Mice were intraperitoneal injected of doxorubicin (DOX) to establish a dilated cardiomyopathy (DCM) model, and then received intravenous injection of either MSC-Exos or PBS as control. Mice receiving MSC-Exos showed improved cardiac function via echocardiography and attenuated cardiac dilation via HE staining, as well as reduced cardiomyocytes apoptosis. Expression levels of inflammatory factors were reduced. And there was a significant decrease of the inflammatory cells infiltration in the MSC-Exos treatment group comparing to the PBS group. Meanwhile, MSC-Exos could remarkably attenuate the pro-inflammatory macrophages amount in both blood and heart, which was proved that MSC-Exos relied on the JAK2-STAT6 pathway mediating macrophages activation. MSC-Exos improved the inflammatory microenvironment of dilated cardiomyopathy by regulating the polarization of the macrophage, which may hold promise for dilated cardiomyopathy clinical therapy. (C) 2018 Elsevier Inc. All rights reserved.