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

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1297-1306
Number of pages10
JournalCirculation Journal
Volume77
Issue number5
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'In vivo differentiation of induced pluripotent stem cell-derived cardiomyocytes'. Together they form a unique fingerprint.

Cite this