title: Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.
abstract: To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (ECs)/vascular mural cells (MCs)], and generate entirely hiPSC-engineered cardiovascular cell sheets, which showed advantageous therapeutic effects in infarcted hearts. The protocol adds to a previous differentiation protocol of CMs by using stage-specific supplementation of vascular endothelial cell growth factor for the additional induction of vascular cells. Using this cell sheet technology, we successfully generated physically integrated cardiac tissue sheets (hiPSC-CTSs). HiPSC-CTS transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, we confirmed that engrafted human cells mainly consisted of CMs in >40% of transplanted rats four weeks after transplantation. Thus, our HiPSC-CTSs show promise for cardiac regenerative therapy.
authors.affiliation: 1] Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan [2] Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Masumoto
authors.affiliation: 1] Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan [2] Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikuno
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors.forename: Jun K
authors.initials: JK
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation; D006321:Heart; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D012038:Regeneration; D023822:Tissue Engineering