Skip to main content

Advertisement

SpringerLink
Log in

Tumorigenesis in cells derived from induced pluripotent stem cells

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Induced pluripotent stem (iPS) cells are an attractive source for potential cell-replacement therapy. However, transplantation of differentiated products harbors the risk of teratoma formation, presenting a serious health risk. Thus, we characterized Nanog-expressing (undifferentiated) cells remaining after induction of differentiation by cytological examination. To induce differentiation of iPS cells, we generated embryoid bodies (EBs) derived from iPS cells carrying a Nanog–green fluorescent protein (GFP) reporter and then injected GFP-positive and GFP-negative EBs into nude mice. GFP-positive EB transplantation resulted in the formation of immature teratoma grade 3, but no tumors were induced by GFP-negative EB. GFP-positive cells revealed significantly lower cytoplasmic area and higher nucleus/cytoplasm ratio than those of GFP-negative cells. Our results suggest that morphological analysis might be a useful method for distinguishing between tumorigenic and nontumorigenic iPS cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med. 2008;3:1–5.

    Article  PubMed  Google Scholar 

  2. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–6.

    Article  CAS  PubMed  Google Scholar 

  3. Tsuji O, Miura K, Okada Y, et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci USA. 2010;107:12704–9.

    Article  CAS  PubMed  Google Scholar 

  4. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  PubMed  Google Scholar 

  5. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  6. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  7. Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol. 2009;27:743–5.

    Article  CAS  PubMed  Google Scholar 

  8. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.

    Article  CAS  PubMed  Google Scholar 

  9. Silva J, Nichols J, Theunissen TW, et al. Nanog is the gateway to the pluripotent ground state. Cell. 2009;138:722–37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kuroda T, Yasuda S, Kusakawa S, et al. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells. PLoS One. 2012;7:e37342.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113:643–55.

    Article  CAS  PubMed  Google Scholar 

  12. Chou YF, Chen HH, Eijpe M, et al. The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells. Cell. 2008;135:449–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Kanatsu-Shinohara M, Inoue K, Lee J, et al. Generation of pluripotent stem cells from neonatal mouse testis. Cell. 2004;119:1001–12.

    Article  CAS  PubMed  Google Scholar 

  14. Wernig M, Zhao JP, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA. 2008;105:5856–61.

    Article  CAS  PubMed  Google Scholar 

  15. Rosai J. Ackerman’s surgical pathology (vol 1). 8th ed. St Louis: Mosby-Year Book; 1996.

    Google Scholar 

  16. Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Cancer. 1976;37:2359–72.

    Article  CAS  PubMed  Google Scholar 

  17. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 2008;322:949–53.

    Article  CAS  PubMed  Google Scholar 

  18. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26:101–6.

    Article  CAS  PubMed  Google Scholar 

  19. Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S. Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci USA. 2010;107:14152–7.

    Article  CAS  PubMed  Google Scholar 

  20. Zhou W, Freed CR. Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells. 2009;27:2667–74.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Satoshi Tomiyasu, Naofumi Hosoda, Atsushi Tomioka, Yukihiko Osawa, Hirotoshi Mochida, Rena Furumoto, and Shiori Tochihara (Graduate School of Science and Industrial Technology, Kurashiki University of Science and the Arts) for their contributions to this study.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Chemical Technology, Graduate School of Science and Industrial Technology, Kurashiki University of Science and the Arts, Kurashiki, Japan

    Makoto Nishimori, Yasuyuki Miyake, Takuya Sakaguchi & Eiji Ohno

  2. Department of Medical Life Science, College of Life Science, Kurashiki University of Science and the Arts, 2640 Nishinoura Tsurajima-cho, Kurashiki, Okayama, 712-8505, Japan

    Hiromasa Yakushiji, Michihiro Mori, Tomoyuki Miyamoto, Takahiro Yaguchi, Setsuyo Ohno, Yasuyuki Miyake, Takuya Sakaguchi & Eiji Ohno

  3. Kake Institute of Cytopathology, Okayama, Japan

    Hiromasa Yakushiji, Michihiro Mori, Tomoyuki Miyamoto, Setsuyo Ohno, Yasuyuki Miyake, Takuya Sakaguchi & Eiji Ohno

  4. Cytopathology and Gynecology, Osaka Center for Cancer and Cardiovascular Diseases Prevention, Osaka, Japan

    Masatsugu Ueda

Authors
  1. Makoto Nishimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiromasa Yakushiji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michihiro Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoyuki Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takahiro Yaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Setsuyo Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuyuki Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takuya Sakaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masatsugu Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eiji Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eiji Ohno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishimori, M., Yakushiji, H., Mori, M. et al. Tumorigenesis in cells derived from induced pluripotent stem cells. Human Cell 27, 29–35 (2014). https://doi.org/10.1007/s13577-013-0078-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-013-0078-3

Keywords

Search

Navigation