In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

• Yu Tao

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science

• Miyagawa Shigeru

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Miki Kenji

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Saito Atsuhiro

  Medical Center for Translational Research, Osaka University Hospital

• Fukushima Satsuki

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Higuchi Takahiro

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Kawamura Masashi

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Kawamura Takuji

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Ito Emiko

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Kawaguchi Naomasa

  Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science

• Sawa Yoshiki

  Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine

• Matsuura Nariaki

  Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science

Abstract

Background: Induced pluripotent stem cells (iPSCs) hold promise for a new era in treating heart failure. However, the functional microstructure of iPSC-derived cardiomyocytes (iPSC-CMs) and their ability to attach to the extracellular matrix of the recipient myocardium require further elucidation. Thus, we analyzed the functional microstructure and adhesion molecules of iPSC-CM. Methods and Results: Immunostaining analysis showed that iPSC-CMs were similar to neonatal cardiomyocytes (CMs) in expressing the cytoskeletal proteins myosin heavy chain (MHC), myosin light chain (MLC) 2a, MLC2v, and especially β-MHC (a neonatal CM marker), as well as the adhesion molecules N-cadherin, α7-integrin, dystrophin, α-dystroglycan, α-sarcoglycan, and laminin-α2. Electron microscopy showed abundant myofibrillar bundles with transverse Z-bands and a developed mitochondrial structure in both iPSC-CMs and neonatal CMs, although the iPSC-CMs contained fewer mitochondria with lower-density cristae. When transplanted from in vitro conditions to nude rat hearts, iPSC-CMs acquired the ability to express α-MHC, a molecule specific to adult CMs. Mechanical stretch or stimulation by insulin-like growth factor-1 enhanced the α-MHC expression in iPSC-CMs in vitro. Conclusions: Our findings in vitro and in vivo indicate that CMs derived from iPSCs contain cardiac-specific organelles and adhesion systems. These results indicate that iPSC-derived CMs may be useful in new cell therapies for heart failure.  (Circ J 2013; 77: 1297–1306)<br>

Journal

• Circulation Journal

  Circulation Journal 77 (5), 1297-1306, 2013

  The Japanese Circulation Society

Keywords

• Adhesion molecules
• Cardiomyocyte differentiation
• Cytoskeleton
• Induced pluripotent stem cells
• Ultrastructure

Details

• CRID: 1390282680082215296
• NII Article ID: 10031151394
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-12-0977
• COI: 1:CAS:528:DC%2BC3sXotFykurw%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 23392122
• Web Site: https://www.jstage.jst.go.jp/article/circj/77/5/77_CJ-12-0977/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014093390
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed