Elimination of undifferentiated human embryonic stem cells by cardiac glycosides

Abstract 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 i...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/542a27d04f554729a165d891f3827aa9
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spelling	oai:doaj.org-article:542a27d04f554729a165d891f3827aa92021-12-02T15:05:22ZElimination of undifferentiated human embryonic stem cells by cardiac glycosides10.1038/s41598-017-05616-22045-2322https://doaj.org/article/542a27d04f554729a165d891f3827aa92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05616-2https://doaj.org/toc/2045-2322Abstract 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.Yu-Tsen LinCheng-Kai WangShang-Chih YangShu-Ching HsuHsuan LinFang-Pei ChangTzu-Chien KuoChia-Ning ShenPo-Ming ChiangMichael HsiaoFrank Leigh LuJean LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Yu-Tsen Lin
title	Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
title_short	Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
title_full	Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
title_fullStr	Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
title_full_unstemmed	Elimination of undifferentiated human embryonic stem cells by cardiac glycosides
title_sort	elimination of undifferentiated human embryonic stem cells by cardiac glycosides
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/542a27d04f554729a165d891f3827aa9
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_version_	1718388829074751488

Elimination of undifferentiated human embryonic stem cells by cardiac glycosides

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