Cell Sheet-Based Myocardial Tissue Engineering: New Hope for Damaged Heart Rescue

Regenerative therapy has currently emerged as one of the most promising treatments for the patients suffering from severe heart failure. Several cell therapies by direct injection have been already clinically performed. However, significant cell loss due to physical strain, primary hypoxia or cell wash-out has become problematic. To overcome this obstacle, tissue engineered myocardial patch transplantation has been examined as the second generation cell therapy. Furthermore several research groups have challenged to engineer pulsatile myocardial tissues/organs using beating cardiomyocytes. Among several tissue engineering technologies, we have developed cell sheet-based tissue engineering, which utilize two-dimensional (2-D) cell sheets harvested from temperature-responsive culture surfaces and create threedimensional (3-D) tissues by stacking cell sheets without generally utilized scaffolds. Several types of cell sheet-based patches have improved damaged heart function in rat, canine and pig models. Stacked cardiomyocyte sheets simultaneously beat in macroscopic view both in vitro and in vivo and revealed characteristic structures of native heart tissue. As a possible solution for scaling up, multi-step transplantation of triple-layer cell sheets was performed and finally, 10-time transplantations have realized about 1 mm-thick functional myocardial tissue. As further advanced therapy, functional myocardial tubes have been also engineered by wrapping cell sheets. Cell sheet-based tissue engineering should have enormous potential in myocardial tissue regenerative medicine and rescue many patients suffering severe heart failure.