Elimination of undifferentiated human embryonic stem cells by cardiac glycosides

被引:0
作者
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
机构
[1] National Defense Medical Center,Graduate Institute of Life Sciences
[2] Academia Sinica,Genomics Research Center
[3] National Yang-Ming University,Institute of Biochemistry and Molecular Biology
[4] National Health Research Institute,National Institute of Infectious Diseases and Vaccinology
[5] National Taiwan University Hospital and National Taiwan University Medical College,Department of Pediatrics
[6] National Yang-Ming University,Department of Biotechnology and Laboratory Science in Medicine
[7] National Cheng Kung University,Institute of Clinical Medicine
[8] National Taiwan University,Genomics and System Biology Program, College of Life Science
[9] National RNAi Platform,National Core Facility Program for Biotechnology
[10] Tzu Chi University,Department of Life Science
来源
Scientific Reports | / 7卷
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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.
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