The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes
Open accessAbstract
Recent withdrawals of prescription drugs from clinical use because of unexpected side effects on the heart have highlighted the need for more reliable cardiac safety pharmacology assays. Block of the human Ether-a-go go Related Gene (hERG) ion channel in particular is associated with life-threatening arrhythmias, such as Torsade de Pointes (TdP). Here we investigated human cardiomyocytes derived from pluripotent (embryonic) stem cells (hESC) as a renewable, scalable, and reproducible system on which to base cardiac safety pharmacology assays. Analyses of extracellular field potentials in hESC-derived cardiomyocytes (hESC-CM) and generation of derivative field potential duration (FPD) values showed dose-dependent responses for 12 cardiac and noncardiac drugs. Serum levels in patients of drugs with known effects on QT interval overlapped with prolonged FPD values derived from hESC-CM, as predicted. We thus propose hESC-CM FPD prolongation as a safety criterion for preclinical evaluation of new drugs in development. This is the first study in which dose responses of such a wide range of compounds on hESC-CM have been generated and shown to be predictive of clinical effects. We propose that assays based on hESC-CM could complement or potentially replace some of the preclinical cardiac toxicity screening tests currently used for lead optimization and further development of new drugs.
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Self-citationMultiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions
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Stem-cell-based therapy and lessons from the heart
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Self-citationIncreased Cardiomyocyte Differentiation from Human Embryonic Stem Cells in Serum‐Free Cultures
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Self-citationHERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine
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Long QT syndrome: from channels to cardiac arrhythmias
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Genetics of acquired long QT syndrome
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Cited by
Burridge, P. W., Keller, G., Gold, J. D., & Wu, J. C. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2011.12.013 · Cited by 670
Fishman, G. I., Chugh, S. S., DiMarco, J. P., Albert, C. M., Anderson, M. E., Bonow, R. O., Buxton, A. E., Chen, P.-S., Estes, M., Jouven, X., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.976092 · Cited by 614
Liang, P., Lan, F., Lee, A. S., Gong, T., Sanchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.001883 · Cited by 537
Lewis-Israeli, Y. R., Wasserman, A. H., Gabalski, M. A., Volmert, B. D., Ming, Y., Ball, K. A., Yang, W., Zou, J., Ni, G., Pajares, N., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25329-5 · Cited by 536
Small molecule absorption by PDMS in the context of drug response bioassays
van Meer, B. J., de Vries, H., Firth, K. S. A., van Weerd, J., Tertoolen, L. G. J., Karperien, H. B. J., Jonkheijm, P., Denning, C., IJzerman, A. P., & Mummery, C. L. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.11.062 · Cited by 502
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Metadata
- Authors
- Braam, S. R., Tertoolen, L., van de Stolpe, A., Meyer, T., Passier, R., & Mummery, C. L.
- Venue
- Stem Cell Research
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 4
- Issue
- 2
- Pages
- 107-116
- ISSN
- 1873-5061 (ISSN-L)
- OpenAlex
- W2031383358
- Cited by
- 368
- References
- 34
- FWCI
- 17.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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