Cell sheet technology for cardiac tissue engineering.

Myocardial tissue regeneration including isolated cell transplantation and recruitment of bone marrow stem cells via cytokines have now emerged as one of the most promising treatments for patients suffering from severe heart failure. As therapy advances, the challenge to engineer three-dimensional (3-D) myocardial tissue grafts has also started. Tissue engineering has currently been based on the technology using 3-D biodegradable scaffolds as alternatives for extracellular matrix (ECM). However, insufficient cell migration into the scaffolds and inflammatory reaction due to scaffold biodegradation remain problems to be solved. By contrast, we have proposed novel tissue engineering technology layering cell sheets to construct 3-D functional tissues without any artificial biodegradable scaffolds. Electrical and morphological communications are established between layered cardiomyocyte sheets, resulting in simultaneous beating 3-D myocardial tissues both in vitro and in vivo. Layered cardiomyocyte sheets in vivo present long survival and functional improvement in accordance with host growth. For vascularization problems, multi-step transplantation of layered cardiomyocyte sheets overcame the thickness limitation of bio-engineered constructs. Cell sheet technology should have enormous potential for engineering clinically applicable myocardial tissues.