title: Enhancing Human Cardiomyocyte Differentiation from Induced Pluripotent Stem Cells with Trichostatin A.
abstract: Human induced pluripotent stem (iPS) cells are a promising source of autologous cardiomyocytes to repair and regenerate myocardium for treatment of heart disease. In this study, we describe a method for enhanced cardiomyocyte production from human iPS cells by treating embryoid bodies with a histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and bone morphogenetic protein (BMP)-4. The resulting cardiomyocytes expressed cardiac-specific transcription factors and contractile proteins at both gene and protein levels. Functionally, the contractile embryoid bodies (EBs) displayed calcium cycling and were responsive to the chronotropic agents isoprenaline (0.1 μM) and carbachol (1 μM). The cardiomyocytes derived from human iPS cells may be used to engineer functional cardiac muscle tissue for studying pathophysiology of cardiac disease, for drug discovery test beds, and potentially for generation of cardiac grafts to surgically replace damaged myocardium.
authors.affiliation: Department of Surgery, O'Brien Institute, University of Melbourne, 42 Fitzroy Street, Fitzroy, VIC, 3065, Australia. maxlim@unimelb.edu.au.
authors.forename: Shiang Y
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Department of Surgery, O'Brien Institute, University of Melbourne, 42 Fitzroy Street, Fitzroy, VIC, 3065, Australia.
authors.forename: Priyadharshini
authors.initials: P
authors.lastname: Sivakumaran
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.|Department of Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Crombie
authors.affiliation: Department of Surgery, O'Brien Institute, University of Melbourne, 42 Fitzroy Street, Fitzroy, VIC, 3065, Australia.|Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.|Department of Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.|Department of Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
authors.affiliation: Department of Surgery, O'Brien Institute, University of Melbourne, 42 Fitzroy Street, Fitzroy, VIC, 3065, Australia. rodney.dilley@uwa.edu.au.|Ear Science Institute Australia, University of Western Australia, Nedlands, Crawley, WA, Australia. rodney.dilley@uwa.edu.au.|Ear Sciences Centre, School of Surgery, The University of Western Australia (M509), 35 Stirling Highway, Crawley, WA, 6009, Australia. rodney.dilley@uwa.edu.au.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Dilley
mesh_terms: D028341:Activins / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D058732:Embryoid Bodies / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology; D052816:Foreskin / Q000166:cytology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D007231:Infant, Newborn; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D006877:Hydroxamic Acids; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; C012589:trichostatin A; D002217:Carbachol; D007545:Isoproterenol
keywords: Cardiac tissue engineering; Cardiomyocyte; Differentiation; Efficiency; Epigenetic; Induced pluripotent stem cells; Trichostatin A