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-Min Chiang, Michael Hsiao, Frank Leigh Lu, Jean Lu

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article number5289
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Cardiac Glycosides
Digoxin
Pluripotent Stem Cells
Teratoma
Proscillaridin
Mesenchymal Stromal Cells
Endothelium
Cell Differentiation
Stem Cells
Bone Marrow
lanatoside C
Human Embryonic Stem Cells
Safety
Neurons
Injections
Pharmaceutical Preparations
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lin, Y. T., Wang, C. K., Yang, S. C., Hsu, S. C., Lin, H., Chang, F. P., ... 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
Lin, Yu Tsen ; Wang, Cheng Kai ; Yang, Shang Chih ; Hsu, Shu Ching ; Lin, Hsuan ; Chang, Fang Pei ; Kuo, Tzu Chien ; Shen, Chia Ning ; Chiang, Po-Min ; Hsiao, Michael ; Lu, Frank Leigh ; Lu, Jean. / Elimination of undifferentiated human embryonic stem cells by cardiac glycosides. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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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.",
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Lin, YT, Wang, CK, Yang, SC, Hsu, SC, Lin, H, Chang, FP, Kuo, TC, Shen, CN, Chiang, P-M, Hsiao, M, Lu, FL & Lu, J 2017, 'Elimination of undifferentiated human embryonic stem cells by cardiac glycosides', Scientific reports, vol. 7, no. 1, 5289. https://doi.org/10.1038/s41598-017-05616-2

Elimination of undifferentiated human embryonic stem cells by cardiac glycosides. / Lin, Yu Tsen; Wang, Cheng Kai; Yang, Shang Chih; Hsu, Shu Ching; Lin, Hsuan; Chang, Fang Pei; Kuo, Tzu Chien; Shen, Chia Ning; Chiang, Po-Min; Hsiao, Michael; Lu, Frank Leigh; Lu, Jean.

In: Scientific reports, Vol. 7, No. 1, 5289, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Lin, Yu Tsen

AU - Wang, Cheng Kai

AU - Yang, Shang Chih

AU - Hsu, Shu Ching

AU - Lin, Hsuan

AU - Chang, Fang Pei

AU - Kuo, Tzu Chien

AU - Shen, Chia Ning

AU - Chiang, Po-Min

AU - Hsiao, Michael

AU - Lu, Frank Leigh

AU - Lu, Jean

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