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Electrical Stimulation Promotes Maturation of Cardiomyocytes Derived from Human Embryonic Stem Cells

Overview of attention for article published in Journal of Cardiovascular Translational Research, October 2013
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Title
Electrical Stimulation Promotes Maturation of Cardiomyocytes Derived from Human Embryonic Stem Cells
Published in
Journal of Cardiovascular Translational Research, October 2013
DOI 10.1007/s12265-013-9510-z
Pubmed ID
Authors

Yau-Chi Chan, Sherwin Ting, Yee-Ki Lee, Kwong-Man Ng, Jiao Zhang, Zi Chen, Chung-Wah Siu, Steve K. W. Oh, Hung-Fat Tse

Abstract

While human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes, their immature phenotypes limit their therapeutic application for myocardial regeneration. We sought to determine whether electrical stimulation could enhance the differentiation and maturation of hESC-derived cardiomyocytes. Cardiac differentiation was induced in a HES3 hESC line via embryoid bodies formation treated with a p38 MAP kinase inhibitor. Detailed molecular and functional analysis were performed in those hESC-derived cardiomyocytes cultured for 4 days in the absence or presence of electrical field stimulation (6.6 V/cm, 1 Hz, and 2 ms pulses) using an eight-channel C-Pace stimulator (Ion-Optics Co., MA). Upon electrical stimulation, quantitative polymerase chain reaction demonstrated significant upregulation of cardiac-specific gene expression including HCN1, MLC2V, SCN5A, SERCA, Kv4.3, and GATA4; immunostaining and flow cytometry analysis revealed cellular elongation and an increased proportion of troponin-T positive cells (6.3 ± 1.2% vs. 15.8 ± 2.1%; n = 3, P < 0.01). Electrophysiological studies showed an increase in the proportion of ventricular-like hESC-derived cardiomyocytes (48 vs. 29%, P < 0.05) with lengthening of their action potential duration at 90% repolarization (387.7 ± 35.35; n = 11 vs. 291.8 ± 20.82; n = 10, P < 0.05) and 50% repolarization (313.9 ± 27.94; n = 11 vs. 234.0 ± 16.10; n = 10, P < 0.05) after electrical stimulation. Nonetheless, the membrane diastolic potentials and action potential upstrokes of different hESC-derived cardiomyocyte phenotypes, and the overall beating rate remained unchanged (all P > 0.05). Fluorescence confocal imaging revealed that electrical stimulation significantly increased both spontaneous and caffeine-induced calcium flux in the hESC-derived cardiomyocytes (approximately 1.6-fold for both cases; P < 0.01). In conclusion, electrical field stimulation increased the expression of cardiac-specific genes and the yield of differentiation, promoted ventricular-like phenotypes, and improved the calcium handling of hESC-derived cardiomyocytes.

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Mendeley readers

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The data shown below were compiled from readership statistics for 258 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 <1%
France 1 <1%
India 1 <1%
United Kingdom 1 <1%
United States 1 <1%
Unknown 253 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 63 24%
Student > Master 30 12%
Student > Bachelor 28 11%
Researcher 26 10%
Student > Doctoral Student 16 6%
Other 36 14%
Unknown 59 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 44 17%
Agricultural and Biological Sciences 39 15%
Engineering 39 15%
Medicine and Dentistry 28 11%
Materials Science 8 3%
Other 34 13%
Unknown 66 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 October 2013.
All research outputs
#18,351,676
of 22,727,570 outputs
Outputs from Journal of Cardiovascular Translational Research
#433
of 575 outputs
Outputs of similar age
#154,372
of 207,109 outputs
Outputs of similar age from Journal of Cardiovascular Translational Research
#4
of 6 outputs
Altmetric has tracked 22,727,570 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 575 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 207,109 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.