title: In vivo differentiation of induced pluripotent stem cell-derived cardiomyocytes.
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.
  
  
  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.
authors: Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, and Medical Center for Translational Research, Osaka University Hospital, Suita, Japan.
authors: Tao
authors: T
authors: Yu
authors: Shigeru
authors: S
authors: Miyagawa
authors: Kenji
authors: K
authors: Miki
authors: Atsuhiro
authors: A
authors: Saito
authors: Satsuki
authors: S
authors: Fukushima
authors: Takahiro
authors: T
authors: Higuchi
authors: Masashi
authors: M
authors: Kawamura
authors: Takuji
authors: T
authors: Kawamura
authors: Emiko
authors: E
authors: Ito
authors: Naomasa
authors: N
authors: Kawaguchi
authors: Yoshiki
authors: Y
authors: Sawa
authors: Nariaki
authors: N
authors: Matsuura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D005260:Female; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation* / Q000648:ultrastructure; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation* / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018994:Myosin Light Chains; D007334:Insulin-Like Growth Factor I; D018995:Myosin Heavy Chains