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

研究成果: Article

4 引文 (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

指紋

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

引用此文

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. 於: Scientific reports. 2017 ; 卷 7, 編號 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, 卷 7, 編號 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.

於: Scientific reports, 卷 7, 編號 1, 5289, 01.12.2017.

研究成果: Article

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AU - Chang, Fang Pei

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AU - Shen, Chia Ning

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AU - Lu, Frank Leigh

AU - Lu, Jean

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