title: Energy utilization of induced pluripotent stem cell-derived cardiomyocyte in Fabry disease.
abstract: BACKGROUND
  Fabry disease (FD) is a lysosomal storage disease in which glycosphingolipids (GB3) accumulate in organs of the human body, leading to idiopathic hypertrophic cardiomyopathy and target organ damage. Its pathophysiology is still poorly understood.
  
  
  OBJECTIVE
  We aimed to generate patient-specific induced pluripotent stem cells (iPSC) from FD patients presenting cardiomyopathy to determine whether the model could recapitulate key features of the disease phenotype and to investigate the energy metabolism in Fabry disease.
  
  
  METHODS
  Peripheral blood mononuclear cells from a 30-year-old Chinese man with a diagnosis of Fabry disease, GLA gene (IVS4+919G>A) mutation were reprogrammed into iPSCs and differentiated into iPSC-CMs and energy metabolism was analyzed in iPSC-CMs.
  
  
  RESULTS
  The FD-iPSC-CMs recapitulated numerous aspects of the FD phenotype including reduced GLA activity, cellular hypertrophy, GB3 accumulation and impaired contractility. Decreased energy metabolism with energy utilization shift to glycolysis was observed, but the decreased energy metabolism was not modified by enzyme rescue replacement (ERT) in FD-iPSCs-CMs.
  
  
  CONCLUSIONS
  This model provided a promising in vitro model for the investigation of the underlying disease mechanism and development of novel therapeutic strategies for FD. This potential remedy for enhancing the energetic network and utility efficiency warrants further study to identify novel therapies for the disease.
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Jie
authors.initials: SJ
authors.lastname: Chou
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Yu
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pharmacology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yuh-Lih
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Yeh
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University and Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jiin-Cherng
authors.initials: JC
authors.lastname: Yen
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yung-Yang
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University and Department of Biotechnology, Asia University, Taichung, Taiwan; Department of Emergent Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: University of California Irvine Diabetes Center and Department of Medicine, Irvine, CA 92697, United States.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: shchiou@vghtpe.gov.tw.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Heath Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: hbleu@vghtpe.gov.tw.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology*; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D008297:Male; D016513:Mice, SCID; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype