Elimination of undifferentiated human embryonic stem cells by cardiac glycosides

Yu Tsen Lin, Cheng Kai Wang, Shang Chih Yang, Shu Ching Hsu, Hsuan Lin, Fang Pei Chang, Tzu Chien Kuo, Chia Ning Shen, Po Ming Chiang, Michael Hsiao, Frank Leigh Lu, Jean Lu

研究成果: Article

7 引文 斯高帕斯(Scopus)

摘要

An important safety concern in the use of human pluripotent stem cells (hPSCs) is tumorigenic risk, because these cells can form teratomas after an in vivo injection at ectopic sites. Several thousands of undifferentiated hPSCs are sufficient to induce teratomas in a mouse model. Thus, it is critical to remove all residue-undifferentiated hPSCs that have teratoma potential before the clinical application of hPSC-derived cells. In this study, our data demonstrated the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C, bufalin, and proscillaridin A, in human embryonic stem cells (hESCs). This phenomenon was not observed in human bone marrow mesenchymal stem cells (hBMMSCs). Most importantly, digoxin and lanatoside C did not affect the stem cells' differentiation ability. Consistently, the viability of the hESC-derived MSCs, neurons, and endothelium cells was not affected by the digoxin and lanatoside C treatment. Furthermore, the in vivo experiments demonstrated that digoxin and lanatoside C prevented teratoma formation. To the best of our knowledge, this study is the first to describe the cytotoxicity and tumor prevention effects of cardiac glycosides in hESCs. Digoxin and lanatoside C are also the first FDA-approved drugs that demonstrated cytotoxicity in undifferentiated hESCs.

原文English
文章編號5289
期刊Scientific reports
7
發行號1
DOIs
出版狀態Published - 2017 十二月 1

All Science Journal Classification (ASJC) codes

  • General

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    Lin, Y. T., Wang, C. K., Yang, S. C., Hsu, S. C., Lin, H., Chang, F. P., Kuo, T. C., Shen, C. N., Chiang, P. M., Hsiao, M., Lu, F. L., & Lu, J. (2017). Elimination of undifferentiated human embryonic stem cells by cardiac glycosides. Scientific reports, 7(1), [5289]. https://doi.org/10.1038/s41598-017-05616-2