In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Tao Yu; Shigeru Miyagawa; Kenji Miki; Atsuhiro Saito; Satsuki Fukushima; Takahiro Higuchi; Masashi Kawamura; Takuji Kawamura; Emiko Ito; Naomasa Kawaguchi; Yoshiki Sawa; Nariaki Matsuura

doi:10.1253/circj.CJ-12-0977

Regenerative Medicine

In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Tao Yu, Shigeru Miyagawa, Kenji Miki, Atsuhiro Saito, Satsuki Fukushima, Takahiro Higuchi, Masashi Kawamura, Takuji Kawamura, Emiko Ito, Naomasa Kawaguchi, Yoshiki Sawa, Nariaki Matsuura

Author information

Tao Yu
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
Shigeru Miyagawa
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Kenji Miki
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Atsuhiro Saito
Medical Center for Translational Research, Osaka University Hospital
Satsuki Fukushima
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Takahiro Higuchi
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Masashi Kawamura
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Takuji Kawamura
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Emiko Ito
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Naomasa Kawaguchi
Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science
Yoshiki Sawa
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine
Nariaki Matsuura
Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science

Keywords: Adhesion molecules, Cardiomyocyte differentiation, Cytoskeleton, Induced pluripotent stem cells, Ultrastructure

JOURNAL FREE ACCESS

2013 Volume 77 Issue 5 Pages 1297-1306

DOI https://doi.org/10.1253/circj.CJ-12-0977

Browse “Advance online publication” version

Details

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)

Corresponding author

Register with J-STAGE for free!