Effects of exosomes from human umbilical cord mesenchymal stem cell on cardiac function in rats with dilated cardiomyopathy induced by Adriamycin

Abstract Background Dilated cardiomyopathy (DCM) is one of the most common cardiomyopathies in children, but we have no effective method to treat it. In recent years,the application of human umbilical cord mesenchymal stem cell (hucMSC) therapy in DCM has made a great progress, whileits mechanism remains unknown. The paracrine of hucMSCs has attracted attention as the main mechanism. In this study we explore the effect of the human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) on the cardiac function in rat models with DCM that is induced by Adriamycin. Methods Sprague-Dawley rats were intraperitoneally injected with Adriamycin to establish aDCM model. HucMSC-Ex were injected through the tail vein in the DCM group and phosphate-buffered saline (PBS) was injected in theDCMcontrolgroup.The rats were monitored for 2 weeks and thecardiac function was evaluated using thecardiac ultrasound.The pathological changes of the myocardium were observed usingimmunohistochemistry. Western blot and real-time fluorescent quantitative PCR were used to detect the expression of Smad3, alpha smooth muscle actin (α-SMA) and I type collagen (COLI)in the myocardial tissue amongthe groups of rats.Finally, the ultrastructure of the myocardium was observed using electron microscopy. High throughput sequencing was performed on the ventricular muscles in each group. Result High-throughput sequencing results show that after the treatment with hucMSC-Ex, the level of myocardial Scn5a in the myocardium significantly increased (P < 0.05). RT-PCR shows that the level of Lmod2 also significantly increased.The expression of Smad3,α-SMA and COL I was reduced(P < 0.05).The inflammation in the myocardial tissue decreased and the mitochondrial swelling was reduced.The left ventricular ejection function (LVEF) and left ventricular fractional shortening (LVFS)in the rats significantly increased (P < 0.05) and the cardiac function was significantly improved (P < 0.05). Conclusion The treatment with hucMSC-Ex through the tail vein can significantly improve thecardiac function and reduce the degree of myocardial fibrosis induced by Adriamycin.