title: Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells.
abstract: The most radical treatment currently available for severe heart failure is heart transplantation; however, the number of donor hearts is limited. A better approach is to make human cardiac tissues. We developed an original cell sheet-based tissue-engineering technology to fabricate human cardiac tissue by layering myocardial cell sheets. Human induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes to fabricate cardiomyocyte sheets. Initially, three-layer human iPS cardiomyocyte (hiPSCM) sheets were transplanted on subcutaneous tissues of nude rats. Next, to fabricate thicker tissue, three-layer sheets were transplanted on one day, then additional three-layer sheets were transplanted onto them the following day, after the first sheets were vascularized. On day 3, the final three-layer sheets were again transplanted, creating a nine-layer graft (multi-step transplantation procedure). In the last step, six-layer sheets were transplanted on fat tissues of the inguinal portion, which were subsequently resected together with the femoral arteries and veins to make transplantable grafts with connectable vessels. They were then transplanted ectopically to the neck portion of other rats by anastomosing vessels with the host's jugular arteries and veins. Transplanted three-layer hiPSCMs were beating and, histologically, showed a cardiac muscle-like structure with vascular systems. Moreover, transplanted hiPSCMs proliferated and matured in vivo. Significantly thicker tissues were fabricated by a multi-step transplantation procedure. The ectopically transplanted graft survived and continued to beat. We succeeded in fabricating functional human cardiac tissue with cell sheet technology. Transplanting this cardiac tissue may become a new treatment option for severe heart failure. Copyright © 2015 John Wiley & Sons, Ltd.
authors: Department of Cardiac Surgery, University of Tokyo, Japan.|Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Hyoe
authors: H
authors: Komae
authors: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Hidekazu
authors: H
authors: Sekine
authors: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Izumi
authors: I
authors: Dobashi
authors: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Katsuhisa
authors: K
authors: Matsuura
authors: Department of Cardiac Surgery, University of Tokyo, Japan.
authors: Minoru
authors: M
authors: Ono
authors: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Teruo
authors: T
authors: Okano
authors: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
authors: Tatsuya
authors: T
authors: Shimizu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation / Q000648:ultrastructure; D008297:Male; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic; D011916:Rats, Inbred F344; D011923:Rats, Nude
keywords: cardiac tissue; cardiomyocyte; cell sheet; heart failure; iPS cells; transplantaion