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Variation in the safety of induced pluripotent stem cell lines

Nature Biotechnology volume 27, pages 743–745 (2009)Cite this article

Abstract

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.

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Figure 1: SNS formation from mouse iPS cells.
Figure 2: Teratoma formation from SNS.

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References

  1. Takahashi, K. & Yamanaka, S. Cell 126, 663–676 (2006).

    Article  CAS  Google Scholar 

  2. Okita, K., Ichisaka, T. & Yamanaka, S. Nature 448, 313–317 (2007).

    Article  CAS  Google Scholar 

  3. Wernig, M. et al. Nature 448, 318–324 (2007).

    Article  CAS  Google Scholar 

  4. Nakagawa, M. et al. Nat. Biotechnol. 26, 101–106 (2008).

    Article  CAS  Google Scholar 

  5. Wernig, M., Meissner, A., Cassady, J.P. & Jaenisch, R. Cell Stem Cell 2, 10–12 (2008).

    Article  CAS  Google Scholar 

  6. Meissner, A., Wernig, M. & Jaenisch, R. Nat. Biotechnol. 25, 1177–1181 (2007).

    Article  CAS  Google Scholar 

  7. Aoi, T. et al. Science 321, 699–702 (2008).

    Article  CAS  Google Scholar 

  8. Stadtfeld, M., Brennand, K. & Hochedlinger, K. Curr. Biol. 18, 890–894 (2008).

    Article  CAS  Google Scholar 

  9. Silva, J. et al. PLoS Biol. 6, e253 (2008).

    Article  Google Scholar 

  10. Kim, J.B. et al. Nature 454, 646–650 (2008).

    Article  CAS  Google Scholar 

  11. Eminli, S., Utikal, J.S., Arnold, K., Jaenisch, R. & Hochedlinger, K. Stem Cells 26, 2467–2474 (2008).

    Article  CAS  Google Scholar 

  12. Hanna, J. et al. Cell 133, 250–264 (2008).

    Article  CAS  Google Scholar 

  13. Park, I.H. et al. Nature 451, 141–146 (2008).

    Article  CAS  Google Scholar 

  14. Yu, J. et al. Science 318, 1917–1920 (2007).

    Article  CAS  Google Scholar 

  15. Takahashi, K. et al. Cell 131, 861–872 (2007).

    Article  CAS  Google Scholar 

  16. Aasen, T. et al. Nat. Biotechnol. 26, 1276–1284 (2008).

    Article  CAS  Google Scholar 

  17. Loh, Y.H. et al. Blood 113, 5476–5479 (2009).

    Article  CAS  Google Scholar 

  18. Yamanaka, S. Cell 137, 13–17 (2009).

    Article  CAS  Google Scholar 

  19. Meiner, V.L. et al. Proc. Natl. Acad. Sci. USA 93, 14041–14046 (1996).

    Article  CAS  Google Scholar 

  20. Niwa, H., Masui, S., Chambers, I., Smith, A.G. & Miyazaki, J. Mol. Cell. Biol. 22, 1526–1536 (2002).

    Article  CAS  Google Scholar 

  21. Okada, Y. et al. Stem Cells 26, 3086–3098 (2008).

    Article  CAS  Google Scholar 

  22. Yu, J. et al. Science 324, 797–801 (2009).

    Article  CAS  Google Scholar 

  23. Kim, D.H. et al. Cell Stem Cell 4, 472–476 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Abe, S. Yamaguchi, T. Tada, Y. Matsuzaki, T. Sunabori, H. Naka, M. Nishino, H. Higashi, T. Ichisaka and M. Imamura for technical assistance and scientific discussions. We also thank H. Niwa (CDB, RIKEN, JAPAN) for the EB3-ES cells, R. Farese (UCSF, USA) for the RF8 ES cells, A. Miyawaki (BSI, RIKEN, JAPAN) for the Venus gene and H. Miyoshi (BioResource Center, RIKEN, JAPAN) for the lentiviral vectors. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Science and Technology Agency; National Institute of Biomedical Innovation; Japan Society for the Promotion of Science (JSPS), the Ministry of Health, Labor, and Welfare; the General Insurance Association of Japan and Keio Gijuku Academic Development Funds. K.M is supported by Research Fellowships for Young Scientists from JSPS.

Author information

Authors and Affiliations

  1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Kyoko Miura, Takashi Aoi, Aki Okada, Kazutoshi Takahashi, Keisuke Okita, Masato Nakagawa, Michiyo Koyanagi, Koji Tanabe, Mari Ohnuki & Shinya Yamanaka

  2. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

    Kyoko Miura, Masato Nakagawa, Koji Tanabe, Mari Ohnuki & Shinya Yamanaka

  3. Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi, Japan

    Kyoko Miura, Takashi Aoi, Aki Okada, Kazutoshi Takahashi, Keisuke Okita, Masato Nakagawa, Michiyo Koyanagi, Koji Tanabe, Mari Ohnuki & Shinya Yamanaka

  4. Department of Physiology, School of Medicine, Keio University, Tokyo, Japan

    Kyoko Miura, Yohei Okada, Daisuke Ogawa & Hideyuki Okano

  5. Kanrinmaru-Project, School of Medicine, Keio University, Tokyo, Japan

    Yohei Okada

  6. Department of Pathology, School of Medicine, Keio University, Tokyo, Japan

    Eiji Ikeda

  7. Gladstone Institute of Cardiovascular Disease, California, San Francisco, USA

    Shinya Yamanaka

Authors
  1. Kyoko Miura
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  2. Yohei Okada
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  3. Takashi Aoi
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  4. Aki Okada
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  5. Kazutoshi Takahashi
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  6. Keisuke Okita
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  7. Masato Nakagawa
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  8. Michiyo Koyanagi
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  9. Koji Tanabe
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  10. Mari Ohnuki
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  11. Daisuke Ogawa
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  12. Eiji Ikeda
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  13. Hideyuki Okano
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  14. Shinya Yamanaka
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Contributions

K.M. conducted most of the experiments. Y.O., T.A., A.O. and M.N. supported experiments and analyses. K. Takahashi, T.A., K.O., M.K., K. Tanabe and M.O. prepared undifferentiated iPS cells. E.I. and K. Takahashi assisted with the pathological analyses. D.O. assisted in some of the stereotactic transplantations. S.Y. and H.O. supervised the entire project. K.M. and S.Y. wrote the manuscript.

Corresponding authors

Correspondence to Hideyuki Okano or Shinya Yamanaka.

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Supplementary Figures 1–7, Supplementary Tables 1–4 and Supplementary Methods (PDF 4384 kb)

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Miura, K., Okada, Y., Aoi, T. et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 27, 743–745 (2009). https://doi.org/10.1038/nbt.1554

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