Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells
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In view of the therapeutic potential of cardiomyocytes derived from induced pluripotent stem (iPS) cells (iPS‐derived cardiomyocytes), in the present study we investigated in iPS‐derived cardiomyocytes, the functional properties related to [Ca 2+]i handling and contraction, the contribution of the sarcoplasmic reticulum (SR) Ca 2+ release to contraction and the b‐adrenergic inotropic responsiveness. The two iPS clones investigated here were generated through infection of human foreskin fibroblasts (HFF) with retroviruses containing the four human genes: OCT4, Sox2, Klf4 and C‐Myc. Our major findings showed that iPS‐derived cardiomyocytes: (i) express cardiac specific RNA and proteins; (ii) exhibit negative force–frequency relations and mild (compared to adult) post‐rest potentiation; (iii) respond to ryanodine and caffeine, albeit less than adult cardiomyocytes, and express the SR‐Ca 2+ handling proteins ryanodine receptor and calsequestrin. Hence, this study demonstrates that in our cardiomyocytes clones differentiated from HFF‐derived iPS, the functional properties related to excitation–contraction coupling, resemble in part those of adult cardiomyocytes.
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The observation of isoproterenol-induced stroke work reduction is consistent with negative force-frequency relationships observed in tissues based on immature cardiomyocytes, including NRVM and hiPSC-CM.
“Our observation of isoproterenol-induced stroke work reduction (Fig. 3b) is consistent with negative force-frequency relationships observed in tissues based on immature cardiomyocytes, including NRVM71 and hiPSC-CM72.”
From A tissue-engineered scale model of the heart ventricle (2018) · cites this paper as [72]
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- Authors
- Germanguz, I., Sedan, O., Zeevi‐Levin, N., Shtrichman, R., Barak, E., Ziskind, A., Eliyahu, S., Meiry, G., Amit, M., Itskovitz‐Eldor, J., & Binah, O.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Binah, Ofer
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2011-01
- Volume
- 15
- Issue
- 1
- Pages
- 38-51
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC3822492
- OpenAlex
- W2051945150
- Semantic Scholar
- 78518cbc7679530967d8ad894e244db8b27a0988
- Cited by
- 160
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 12 · 2019: 5 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 14 · 2012: 17
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- induced pluripotent stem cells, excitation-contraction coupling, sarcoplasmic reticulum calcium release, ryanodine receptor, calsequestrin, calcium handling, force-frequency relationship, post-rest potentiation, cardiac differentiation, human foreskin fibroblasts, Oct4, SOX2, KLF4, c-Myc, retroviral reprogramming
- MeSH terms
- Kruppel-Like Factor 4, Animals, Caffeine, Calcium, Calsequestrin, Cell Differentiation, Cells, Cultured, Fibroblasts, Fluorescent Antibody Technique, Humans, Male, Myocardial Contraction, RNA, Messenger, Ryanodine, Sarcoplasmic Reticulum, Teratoma, Gene Expression, Proto-Oncogene Proteins c-myc, Mice, SCID, Ryanodine Receptor Calcium Release Channel, Myocytes, Cardiac, Octamer Transcription Factor-3, Mice, Kruppel-Like Transcription Factors, Foreskin, SOXB1 Transcription Factors, Induced Pluripotent Stem Cells
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