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Nature Biotechnology:不同体细胞培育出的iPS细胞安全性存差异

2009.7.13
iPS研究先驱日本京都大学教授山中伸弥教授带领团队在新一期《自然·生物技术》杂志上报告说,动物实验证明,用不同种类的体细胞培育出的诱导多功能干细胞(iPS)移植后使实验鼠出现肿瘤的危险性存在很大差异。

研究人员分别利用小鼠胚胎的皮肤细胞、成年小鼠的胃细胞、尾巴的皮肤细胞以及肝脏细胞培育iPS细胞。利用不同的体细胞和培育方法,研究人员共培育出36种iPS细胞。

接着,他们又使这36种iPS细胞都分化成具备演变成神经能力的细胞,并把这些细胞植入另一些实验鼠的大脑。结果显示,被植入分化细胞来自成年小鼠 尾巴皮肤细胞的实验鼠中有83%体内出现了肿瘤;被植入分化细胞来自于小鼠胚胎皮肤细胞的实验鼠中只有8%出现肿瘤;而如果实验鼠移植的分化细胞来自成年 小鼠的胃细胞,其体内没有出现肿瘤。

研究还发现,利用含有癌症基因的体细胞培育iPS,对肿瘤的发生几率并无显著影响。

诱导多功能干细胞能分化生成各种组织细胞,同时又回避了伦理问题,被视为未来再生医疗的重要材料。上述研究表明,确保iPS细胞对治疗的安全性,最重要的是选择何种体细胞作为培育iPS细胞的原料。(生物谷Bioon.com)

原始出处:

Nature Biotechnology 9 July 2009 | doi:10.1038/nbt.1554

Variation in the safety of induced pluripotent stem cell lines

Kyoko Miura1,2,3,4, Yohei Okada4,5, Takashi Aoi1,3, Aki Okada1,3, Kazutoshi Takahashi1,3, Keisuke Okita1,3, Masato Nakagawa1,2,3, Michiyo Koyanagi1,3, Koji Tanabe1,2,3, Mari Ohnuki1,2,3, Daisuke Ogawa4, Eiji Ikeda6, Hideyuki Okano4 & Shinya Yamanaka1,2,3,7

We evaluated the teratoma-forming propensity of secondary neurospheres (SNS) generated from 36 mouse induced pluripotent stem (iPS) cell lines derived in 11 different ways. Teratoma-formation of SNS from embryonic fibroblast–derived iPS cells was similar to that of SNS from embryonic stem (ES) cells. In contrast, SNS from iPS cells derived from different adult tissues varied substantially in their teratoma-forming propensity, which correlated with the persistence of undifferentiated cells.

1 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
2 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
3 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi, Japan.
4 Department of Physiology, School of Medicine, Keio University, Tokyo, Japan.
5 Kanrinmaru-Project, School of Medicine, Keio University, Tokyo, Japan.
6 Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
7 Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.

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