The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Modeling Doxorubicin-Induced Cardiotoxicity in Human Pluripotent Stem Cell Derived-Cardiomyocytes
Open accessAbstract
Doxorubicin is a highly efficacious anti-cancer drug but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity (DIC) remain incompletely understood. We investigated the characteristics and molecular mechanisms of DIC in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). We found that doxorubicin causes dose-dependent increases in apoptotic and necrotic cell death, reactive oxygen species production, mitochondrial dysfunction and increased intracellular calcium concentration. We characterized genome-wide changes in gene expression caused by doxorubicin using RNA-seq, as well as electrophysiological abnormalities caused by doxorubicin with multi-electrode array technology. Finally, we show that CRISPR-Cas9-mediated disruption of TOP2B, a gene implicated in DIC in mouse studies, significantly reduces the sensitivity of hPSC-CMs to doxorubicin-induced double stranded DNA breaks and cell death. These data establish a human cellular model of DIC that recapitulates many of the cardinal features of this adverse drug reaction and could enable screening for protective agents against DIC as well as assessment of genetic variants involved in doxorubicin response.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Lian, X., Zhang, J., Azarin, S. M., Zhu, K., Hazeltine, L. B., Bao, X., Hsiao, C., Kamp, T. J., & Palecek, S. P. (2013) · Nature Protocols · doi:10.1038/nprot.2012.150 · Cited by 1,748
Lian, X., Hsiao, C., Wilson, G., Zhu, K., Hazeltine, L. B., Azarin, S. M., Raval, K. K., Zhang, J., Kamp, T. J., & Palecek, S. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200250109 · Cited by 1,717
Chemically defined generation of human cardiomyocytes
Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2999 · Cited by 1,606
Mihic, A., Li, J., Miyagi, Y., Gagliardi, M., Li, S.-H., Zu, J., Weisel, R. D., Keller, G., & Li, R.-K. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.052 · Cited by 248
Cited by
Zhao, L., & Zhang, B. (2017) · Scientific Reports · doi:10.1038/srep44735 · Cited by 375
Advanced human developmental toxicity and teratogenicity assessment using human organoid models
Li, M., Gong, J., Gao, L., Zou, T., Kang, J., & Xu, H. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113429 · Cited by 84
Sapp, V., Aguirre, A., Mainkar, G., Ding, J., Adler, E., Liao, R., Sharma, S., & Jain, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-92988-1 · Cited by 40
Metadata
- Authors
- Maillet, A., Tan, K., Chai, X., Sadananda, S. N., Mehta, A., Ooi, J., Hayden, M. R., Pouladi, M. A., Ghosh, S., Shim, W., & Brunham, L. R.
- Venue
- Scientific Reports
- Published
- 2016-05-04
- Volume
- 6
- Issue
- 1
- Pages
- 25333-25333
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2346631874
- Cited by
- 183
- References
- 5
- FWCI
- 16.19
- Type
- journal article
- Language
- en
- Open access
- gold
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- Maillet, A., Tan, K., Chai, X., Sadananda, S. N., Mehta, A., Ooi, J., Hayden, M. R., Pouladi, M. A., Ghosh, S., Shim, W., & Brunham, L. R. (2016). Modeling Doxorubicin-Induced Cardiotoxicity in Human Pluripotent Stem Cell Derived-Cardiomyocytes. Scientific Reports. https://doi.org/10.1038/srep25333
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