At present, cardiac diseases are a major cause of morbidity and mortality in the world. Recently, a cell-based regenerative medicine has appeared as one of the most potential and promising therapies for improving cardiac diseases. As a new generational cell-based regenerative therapy, tissue engineering is focused. Our laboratory has originally developed cell sheet-based scaffold-free tissue engineering. Three-dimensional myocardial tissue fabricated by stacking cardiomyocyte sheets, which are tightly interconnected to each other through gap junctions, beats simultaneously and macroscopically and shows the characteristic structures of native heart tissue. Cell sheet-based therapy cures the damaged heart function of animal models and is clinically applied. Cell sheet-based tissue engineering has a promising and enormous potential in myocardial tissue regenerative medicine and will cure many patients suffering from severe cardiac disease. This paper summarizes cell sheet-based tissue engineering and its satisfactory therapeutic effects on cardiac disease. 1. Introduction Various clinical therapies including drug-based, catheter-based, surgical-based, and medical device-based therapies for cardiac disease are performed and found to elongate the life-span of patients who suffer cardiac disease. However, cardiac disease still remains a major cause of morbidity and mortality in the world, especially in developed countries [1–3]. Some conventional therapies have several problems, for example, the possible risks of side effects, the requirements of special techniques and repeating therapy, immune rejection, donor shortage, infection, and thrombus, and so forth. Therefore, at present, many researchers in various fields including surgery, internal medicine, pharmacology, medical device technology, chemistry, and cell biology, are actively attempting to find possible solutions for the problems and establish new therapies for curing severe cardiac diseases. Cell-based regenerative therapy currently emerges as one of the most promising methods for treating cardiac disease. Regenerative therapy by the direct injection of dissociated cells has been clinically performed, and the modest therapeutic efficacies are confirmed [4–10]. Previous studies in animal models and clinical trials show that many injected cells die after the transplantation and only few transplanted cells are detected in the infarcted myocardium [11, 12]. The poor survival of injected cells hinders more effective therapeutic effects. In addition, the controls of the shape, size, and location of
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