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Variation in the safety of induced pluripotent stem cell lines


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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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.

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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.

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Correspondence to Hideyuki Okano or Shinya Yamanaka.

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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).

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