Myocardial Tissue Regeneration by Cell Sheet Engineering(The 21st COE Symposium on the Frontier Regenerative Medicine)

摘要

Recently, regenerative medicine has been proposed as a new therapy for repairing damaged heart. In direct transplantation of dissociated cells, it is difficult to control shape, size and location of the transplanted grafts. To solve these problems, further advanced therapies to transplant bioengineered 3-dimensional (3-D) myocardial tissue have been investigated. In contrast to popular approach seeding cells onto 3-D biodegradable scaffolds, we have developed novel technology "cell sheet engineering" that layers cell sheets to reconstruct 3-D tissues. By using this technology, neonatal rat cardiomyocyte sheets were successfully layered and electrically communicative pulsatile 3-D myocardial tissues have been engineered. Engineered myocardial tissues grew and survived up to one year in vivo. These bioengineered myocardial tissue grafts improved damaged heart function in animal models. As next step, we have challenged to promote neovascularization in bioengineered myocardial tissues for overcoming the limitation of engineered tissue thickness. One possible idea is layering cell sheets co-cultured with endothelial cells. We confirmed the neovascular promotion when we used co-cultured cell sheets. Another technique is polysurgery of layered cell sheets at enough intervals for neovascularization. The overlaid grafts revealed synchronized beating and thicker (about 1 mm) vascularlized tissues without necrosis. These cell sheetbased technologies might contribute to tissue engineering research field as well as myocardial tissue repair.