Influence of continuous electrical stimulation on development of human cardiomyocytes from induced pluripotent stem cells
AuthorHernández, D; Millard, R; Sivakumaran, P; Kong, A; Mitchell, G; Pebay, A; Sheperd, R; Dusting, G; Lim, S
Source TitleConditioning Medicine
University of Melbourne Author/sPebay, Alice; Millard, Rodney; Sivakumaran, Priyadharshini; Kong, Anne; Mitchell, Geraldine; Dusting, Gregory; Lim, Shiang; Shepherd, Robert; Hernandez De Santiago, Hector
Document TypeJournal Article
CitationsHernández, D., Millard, R., Sivakumaran, P., Kong, A., Mitchell, G., Pebay, A., Sheperd, R., Dusting, G. & Lim, S. (2018). Influence of continuous electrical stimulation on development of human cardiomyocytes from induced pluripotent stem cells. Conditioning Medicine, 1 (6), pp.306-312
Access StatusOpen Access
Regeneration of cardiac tissue remains an ideal approach to restore cardiac function after myocardial infarction. The ability of human induced pluripotent stem cells (iPSCs) to differentiate into bona fide cardiomyocytes also provides a platform for cardiac disease modeling, drug discovery and pharmacological safety testing of new drugs. One of the major limitations for the use of cardiomyocytes derived from iPSCs is that they resemble fetal cardiomyocytes and are immature compared to adult cardiomyocytes. Considering that the developing heart grows in an electric field, we investigated whether electrical stimulation can promote maturation of cardiomyocytes derived from human iPSCs. Two-dimensional cultures of immature cardiomyocytes at day 22 post-differentiation were subjected to continuous electrical stimulation at 200 mV/mm for 7 days using a custom-made electrical stimulator. This long-term electrical stimulation significantly increased the percentage of cardiomyocytes with organized sarcomeres and promoted alignment of cardiomyocytes parallel to the electric field. Electrical stimulation also decreased the circularity index of cardiomyocytes suggesting a more rod-like morphology. In conclusion, long-term continuous electrical stimulation promotes maturation of cardiomyocytes derived from human iPSCs. Mature cardiomyocytes can better recapitulate the pathophysiological conditions of the human heart for more accurate disease modeling and drug testing. Mature cardiomyocytes can also provide a substrate for cardiac regeneration and repair by tissue engineering in the future.
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