Differentiation of Human Embryonic Stem Cells to Cardiomyocytes: Role of Coculture With Visceral Endoderm-Like Cells
Open accessAbstract
Background— Cardiomyocytes derived from human embryonic stem (hES) cells could be useful in restoring heart function after myocardial infarction or in heart failure. Here, we induced cardiomyocyte differentiation of hES cells by a novel method and compared their electrophysiological properties and coupling with those of primary human fetal cardiomyocytes. Methods and Results— hES cells were cocultured with visceral-endoderm (VE)–like cells from the mouse. This initiated differentiation to beating muscle. Sarcomeric marker proteins, chronotropic responses, and ion channel expression and function were typical of cardiomyocytes. Electrophysiology demonstrated that most cells resembled human fetal ventricular cells. Real-time intracellular calcium measurements, Lucifer yellow injection, and connexin 43 expression demonstrated that fetal and hES-derived cardiomyocytes are coupled by gap junctions in culture. Inhibition of electrical responses by verapamil demonstrated the presence of functional α 1c -calcium ion channels. Conclusions— This is the first demonstration of induction of cardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis. It provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomyocyte transplantation therapies.
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Human pluripotent stem cells can be differentiated into ventricular cardiomyocytes that prior work has characterized thoroughly at the single-cell level.
“Human pluripotent stem cells (hPSC) can be specified into ventricular cardiomyocytes (vCM) that have been robustly characterized at the single-cell level [2–5].”
From Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells (2018) · cites this paper as [2]
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- Authors
- Mummery, C., Ward-van Oostwaard, D., Doevendans, P., Spijker, R., van den Brink, S., Hassink, R., van der Heyden, M., Opthof, T., Pera, M., de la Riviere, A. B., Passier, R., & Tertoolen, L.
- Affiliations
- University Medical Center Utrecht (NL)
- From the Hubrecht Laboratory (C.M., D.W.v.O., R.S., S.v.d.B., R.H., R.P., L.T.); the Departments of Medical Physiology (M.v.d.H., T.O.), Cardiothoracic Surgery (R.H., A.B.d.l.R.), and Cardiology (P.D.), University Medical Center Utrecht; and the Interuniversity Cardiology Institute of the Netherlands (C.M., P.D., R.P.), Utrecht, Netherlands; and the Monash Institute of Reproduction and Development, Melbourne Australia (M.P.).
- Venue
- Circulation
- Published
- 2003-06-03
- Volume
- 107
- Issue
- 21
- Pages
- 2733-2740
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W4246928383
- Cited by
- 1,001
- References
- 25
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 10 · 2023: 21 · 2022: 17 · 2021: 31 · 2020: 44 · 2019: 21 · 2018: 34 · 2017: 40 · 2016: 48 · 2015: 57 · 2014: 61 · 2013: 57 · 2012: 79
- FWCI
- 16.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (902-16-193)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- human embryonic stem cells, cardiomyocyte differentiation, electrophysiological properties, electrical coupling, connexin 43, calcium channels, cardiomyocyte transplantation, myocardial infarction, heart failure
- MeSH terms
- Action Potentials, Animals, Antigens, Differentiation, Cell Communication, Cell Differentiation, Cell Line, Endoderm, Fluorescent Dyes, Heart, Humans, Ion Channels, Myocardium, Stem Cells, Viscera, Patch-Clamp Techniques, Coculture Techniques, Cell Lineage, Calcium Signaling, Myocytes, Cardiac, Mice
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