Sutureless transplantation of<i>in vivo</i>priming human mesenchymal stem cell sheet promotes the therapeutic potential for cardiac repair.

Abstract

The heart, contrary to its small size, vigorously pumps oxygen and nutrients to our entire body indeterminably; and thus, its dysfunction could be devastating. Until now, there ave been several major obstacles to applying a cardiac patch for the treatment for myocardial infarction, including poor integration and low engraftment rates, due to the highly-curved surface of the heart and its dynamic nature. Here, we demonstrate a novel way for a comprehensive cardiac repair achieved by the sutureless transplantation of a highly integrable<i>in vivo</i>priming bone marrow mesenchymal stem cell (BMSC) sheet based on the utilization of a highly aligned thermoresponsive nanofiber membrane. Moreover, we developed a BMSC sheet specialized for vascular regeneration through '<i>in-vivo</i>priming' using human umbilical vein endothelial cells. A prolonged secretion of multiple angiogenic cytokines, such as vascular endothelial growth factor, angiopoietin-1, insulin-like growth factor-1, which was observed<i>in vitro</i>from the specialized BMSC sheet seemed to lead a significant improvement in the cardiac function, including intrinsic contractibility and remodeling. In this study, we provide strong evidence that<i>in vivo</i>priming of a human BMSC sheet develops the therapeutic potential for cardiac repair.