title: Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells.
abstract: Background. Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Damián
authors.initials: D
authors.lastname: Hernández
authors.affiliation: Bionics Institute, East Melbourne, VIC 3002, Australia; Medical Bionics Department, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Millard
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, 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 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Raymond C B
authors.initials: RC
authors.lastname: Wong
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Crombie
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia; School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7005, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Helena
authors.initials: H
authors.lastname: Liang
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Sandy S C
authors.initials: SS
authors.lastname: Hung
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
authors.affiliation: Bionics Institute, East Melbourne, VIC 3002, Australia; Medical Bionics Department, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shepherd
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia; Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 3002, Australia; Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Shiang Y
authors.initials: SY
authors.lastname: Lim