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The development of a bioengineered organ germ method

Nature Methods volume 4, pages 227–230 (2007)Cite this article

Abstract

To bioengineer ectodermal organs such as teeth and whisker follicles, we developed a three-dimensional organ-germ culture method. The bioengineered tooth germ generated a structurally correct tooth, after both in vitro organ culture as well as transplantation under a tooth cavity in vivo, showing penetration of blood vessels and nerve fibers. Our method provides a substantial advance in the development of bioengineered organ replacement strategies and regenerative therapies. Please visit methagora to view and post comments on this article

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Figure 1: Generation of a whole tooth using bioengineered tooth germ derived from dissociated single cells in vivo.
Figure 2: Development of the bioengineered incisor in the tooth cavity of adult mice.
Figure 3: Analysis of periodontal ligaments, endothelial cells of tooth blood vessels and neural filaments in a bioengineered tooth.

References

  1. Langer, R.S. & Vacanti, J.P. Sci. Am. 280, 86–89 (1999).

    Article  CAS  Google Scholar 

  2. Brockes, J.P. & Kumar, A. Science 310, 1919–1923 (2005).

    Article  CAS  Google Scholar 

  3. Atala, A. Expert Opin. Biol. Ther. 5, 879–892 (2005).

    Article  CAS  Google Scholar 

  4. Pispa, J. & Thesleff, I. Dev. Biol. 262, 195–205 (2003).

    Article  CAS  Google Scholar 

  5. Thesleff, I. J. Cell Sci. 116, 1647–1648 (2003).

    Article  CAS  Google Scholar 

  6. Tucker, A. & Sharpe, P. Nat. Rev. Genet. 5, 499–508 (2004).

    Article  CAS  Google Scholar 

  7. Sharpe, P.T. & Young, C.S. Sci. Am. 293, 34–41 (2005).

    Article  Google Scholar 

  8. Young, C.S. et al. J. Dent. Res. 81, 695–700 (2002).

    Article  CAS  Google Scholar 

  9. Ohazama, A., Modino, S.A., Miletich, I. & Sharpe, P.T. J. Dent. Res. 83, 518–522 (2004).

    Article  CAS  Google Scholar 

  10. Song, Y. et al. Dev. Dyn. 235, 1334–1344 (2006).

    Article  CAS  Google Scholar 

  11. Hu, B. et al. Tissue Eng. 12, 2069–2075 (2006).

    Article  CAS  Google Scholar 

  12. Steinberg, M.S. Dev. Biol. 180, 377–388 (1996).

    Article  CAS  Google Scholar 

  13. Hata, R.I. Cell Biol. Int. 20, 59–65 (1996).

    Article  CAS  Google Scholar 

  14. Salmivirta, K., Gullberg, D., Hirsch, E., Altruda, F. & Ekblom, P. Dev. Dyn. 205, 104–113 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Okabe (Osaka University) for providing the C57BL/6-TgN (act-EGFP) OsbC14-Y01-FM131 mice. We are also grateful to K. Itoh and M. Sugai (Kyoto University) for critical reading of this manuscript. We also thank to T. Katakai (Kyoto University) and Y. Nishi (Nagahama Institute of Bioscience and Technology) for their valuable discussions and encouragement. This work was partially supported by an “Academic Frontier” Project for Private Universities to Y.T. and T.T. (2003–2007) and by a Grant-in Aid for Scientific Research in Priority Areas (50339131) to T.T. from MEXT Japan.

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Authors and Affiliations

  1. Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Noda, 278-8510, Chiba, Japan

    Kazuhisa Nakao, Ritsuko Morita, Yasumitsu Saji, Kentaro Ishida, Yusuke Tomita, Miho Ogawa, Yasuhiro Tomooka & Takashi Tsuji

  2. Tissue Engineering Research Center, Tokyo University of Science, Noda, 278-8510, Chiba, Japan

    Kazuhisa Nakao, Ritsuko Morita, Yasumitsu Saji, Kentaro Ishida, Yusuke Tomita, Miho Ogawa, Yasuhiro Tomooka & Takashi Tsuji

  3. Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan

    Masahiro Saitoh

Authors
  1. Kazuhisa Nakao
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  2. Ritsuko Morita
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  3. Yasumitsu Saji
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  4. Kentaro Ishida
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  5. Yusuke Tomita
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  6. Miho Ogawa
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  7. Masahiro Saitoh
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  8. Yasuhiro Tomooka
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  9. Takashi Tsuji
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Contributions

K.N. was involved in each of the experiments described in this study. R.M. analyzed the explants that were formed by a combination of normal and GFP-transgenic mouse-derived cells and performed the immunohistochemical analysis shown in Figure 3. Y.S. performed and analyzed the transplantation experiments in both the subrenal capsule and the tooth cavity. K.I. and M.S. performed the in situ hybridization analysis. Y.T. performed the subrenal capsule transplantation experiments and histological analysis. M.O. maintained the in vitro organ cultures and performed whole-mount analysis of the chimeric bioengineered tooth germ. K.N. and T.T. prepared the manuscript. K.N., M.S., Y.T. and T.T. discussed the results and also contributed to the preparation of this manuscript. T.T. designed the experiments.

Corresponding author

Correspondence to Takashi Tsuji.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Effects of cell density and cell compartmentalization between epithelial and mesenchymal cells upon the generation of bioengineered teeth. (PDF 756 kb)

Supplementary Fig. 2

Three-dimensional histological analysis of bioengineered teeth under various developmental conditions. (PDF 644 kb)

Supplementary Fig. 3

Expression of the regulatory genes that function during early tooth development in a bioengineered incisor tooth germ. (PDF 408 kb)

Supplementary Fig. 4

Generation of a reconstituted whisker in vivo from a bioengineered follicle. (PDF 434 kb)

Supplementary Fig. 5

Development and transplantation of individual primordia. (PDF 416 kb)

Supplementary Methods (PDF 27 kb)

Supplementary Note (PDF 24 kb)

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Nakao, K., Morita, R., Saji, Y. et al. The development of a bioengineered organ germ method. Nat Methods 4, 227–230 (2007). https://doi.org/10.1038/nmeth1012

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