Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells

被引：31
|
作者：
Yamashita, Akihiro [1 ]
Liu, Shiying [1 ]
Woltjen, Knut [2 ,3 ]
Thomas, Bradley [1 ]
Meng, Guoliang [1 ]
Hotta, Akitsu [2 ,3 ,5 ,6 ]
Takahashi, Kazutoshi [2 ]
Ellis, James [6 ,7 ]
Yamanaka, Shinya [2 ,3 ,4 ,8 ]
Rancourt, Derrick E. [1 ]
机构：
[1] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada
[2] Kyoto Univ, Dept Reprogramming Sci, Ctr iPS Cell Res & Applicat, Kyoto, Japan
[3] Kyoto Univ, Inst Integrated Cell Mat Sci iCeMS, Kyoto, Japan
[4] Japan Sci & Technol Agcy, Yamanaka iPS Cell Special Project, Kawaguchi, Saitama 3320012, Japan
[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[6] Hosp Sick Children, Toronto, ON M5G 1X8, Canada
[7] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
[8] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA
来源：
SCIENTIFIC REPORTS | 2013年 / 3卷
关键词：
DIFFERENTIATION; LIN28; MYC; TRANSFORMATION; GENERATION;
D O I：
10.1038/srep01978
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Safety is the foremost issue in all human cell therapies, but human induced pluripotent stem cells (iPSCs) currently lack a useful safety indicator. Studies in chimeric mice have demonstrated that certain lines of iPSCs are tumorigenic; however a similar screen has not been developed for human iPSCs. Here, we show that in vitro cartilage tissue engineering is an excellent tool for screening human iPSC lines for tumorigenic potential. Although all human embryonic stem cells (ESCs) and most iPSC lines tested formed cartilage safely, certain human iPSCs displayed a pro-oncogenic state, as indicated by the presence of secretory tumors during cartilage differentiation in vitro. We observed five abnormal iPSC clones amoungst 21 lines derived from five different reprogramming methods using three cellular origins. We conclude that in vitro cartilage tissue engineering is a useful approach to identify abnormal human iPSC lines.
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页数：6
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