Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

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 we...

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Main Authors: Damián Hernández, Rodney Millard, Priyadharshini Sivakumaran, Raymond C. B. Wong, Duncan E. Crombie, Alex W. Hewitt, Helena Liang, Sandy S. C. Hung, Alice Pébay, Robert K. Shepherd, Gregory J. Dusting, Shiang Y. Lim
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1718041
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author Damián Hernández
Rodney Millard
Priyadharshini Sivakumaran
Raymond C. B. Wong
Duncan E. Crombie
Alex W. Hewitt
Helena Liang
Sandy S. C. Hung
Alice Pébay
Robert K. Shepherd
Gregory J. Dusting
Shiang Y. Lim
author_facet Damián Hernández
Rodney Millard
Priyadharshini Sivakumaran
Raymond C. B. Wong
Duncan E. Crombie
Alex W. Hewitt
Helena Liang
Sandy S. C. Hung
Alice Pébay
Robert K. Shepherd
Gregory J. Dusting
Shiang Y. Lim
author_sort Damián Hernández
collection DOAJ
description 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.
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spelling doaj-art-db8a2e5ce9df4d91912a7d6e8fa7c8b82025-02-03T01:09:38ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/17180411718041Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem CellsDamián Hernández0Rodney Millard1Priyadharshini Sivakumaran2Raymond C. B. Wong3Duncan E. Crombie4Alex W. Hewitt5Helena Liang6Sandy S. C. Hung7Alice Pébay8Robert K. Shepherd9Gregory J. Dusting10Shiang Y. Lim11O’Brien Institute Department, St Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, AustraliaBionics Institute, East Melbourne, VIC 3002, AustraliaO’Brien Institute Department, St Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, AustraliaBionics Institute, East Melbourne, VIC 3002, AustraliaO’Brien Institute Department, St Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, AustraliaO’Brien Institute Department, St Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, AustraliaBackground. 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.http://dx.doi.org/10.1155/2016/1718041
spellingShingle Damián Hernández
Rodney Millard
Priyadharshini Sivakumaran
Raymond C. B. Wong
Duncan E. Crombie
Alex W. Hewitt
Helena Liang
Sandy S. C. Hung
Alice Pébay
Robert K. Shepherd
Gregory J. Dusting
Shiang Y. Lim
Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
Stem Cells International
title Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
title_full Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
title_fullStr Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
title_full_unstemmed Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
title_short Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells
title_sort electrical stimulation promotes cardiac differentiation of human induced pluripotent stem cells
url http://dx.doi.org/10.1155/2016/1718041
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