Human umbilical cord-derived stem cell sheets improve left ventricular function in rat models of ischemic heart failure

Introduction: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are among the most promising cell therapy sources used to treat ischemic heart disease. Cell sheet engineering has been used to transplant stem cells and improve their therapeutic effectiveness. We aimed to evaluate the effectiveness of UC-MSC sheets in the treatment of chronic ischemic heart failure. Methods and results: Flow cytometric analysis showed that UC-MSCs were positive for CD73, CD90, and CD105. UC-MSC sheets were produced from UC-MSCs using temperature-responsive culture dishes. Afterward, these sheets were transplanted onto the epicardial surface at the infarct heart in rat models of chronic ischemic heart failure. At four weeks after the transplantation, echocardiography analysis revealed that the cardiac function of the UC-MSC sheets group was significantly better than that of the suspension and myocardial infarction (MI) only groups. Furthermore, histological examinations revealed that the left ventricular remodeling was attenuated compared with the suspension and MI-only groups. In the UC-MSC slice group, the neovascular den and cell size in the infarct margin region were was significantly improved than in the suspension and MI-only groups. Also, the UC-MSC sheets inhibited the PI3K/AKT/mTOR signaling pathway in chronic ischemic heart failure. Conclusions: UC-MSC sheets can maintain cardiac function and attenuate ventricular remodeling in chronic ischemic heart failure, indicating that this strategy would be a promising therapeutic option in the clinical scenario.