Brief Communication | Published:

The development of a bioengineered organ germ method

Nature Methods volume 4, pages 227230 (2007) | Download Citation

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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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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.

Author information

Affiliations

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

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Takashi Tsuji.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Effects of cell density and cell compartmentalization between epithelial and mesenchymal cells upon the generation of bioengineered teeth.

  2. 2.

    Supplementary Fig. 2

    Three-dimensional histological analysis of bioengineered teeth under various developmental conditions.

  3. 3.

    Supplementary Fig. 3

    Expression of the regulatory genes that function during early tooth development in a bioengineered incisor tooth germ.

  4. 4.

    Supplementary Fig. 4

    Generation of a reconstituted whisker in vivo from a bioengineered follicle.

  5. 5.

    Supplementary Fig. 5

    Development and transplantation of individual primordia.

  6. 6.

    Supplementary Methods

  7. 7.

    Supplementary Note

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DOI

https://doi.org/10.1038/nmeth1012

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