• Tao Yu, Shigeru Miyagawa, Kenji Miki, Atsuhiro Saito, Satsuki Fukushima, Takahiro Higuchi, Masashi Kawamura, Takuji Kawamura, Emiko Ito, Naomasa Kawaguchi, Yoshiki Sawa, and Nariaki Matsuura.
• Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, and Medical Center for Translational Research, Osaka University Hospital, Suita, Japan.
• Circ. J. 2013 Jan 1;77(5):1297-306.

BackgroundInduced 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 ResultsImmunostaining 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.ConclusionsOur 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. 

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