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2006 Fiscal Year Final Research Report Summary

Regeneration of tooth germ using dental epithelial stem cells and dental papilla mesenchymal stem cells in rodent incisors

Research Project

Project/Area Number 16390527
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionIwate Medical University (2006)
Osaka University (2004-2005)

Principal Investigator

HARADA Hidemitsu  Iwate Medical University, School of Dentistry, Oral Anatomy II, Professor, 歯学部, 教授 (70271210)

Co-Investigator(Kenkyū-buntansha) OHSHIMA Hayato  Niigata University, Academic Assembly, Institute of Medicine and Dentistry, 医歯学系, 教授 (70251824)
ISHIZEKI Kiyoto  Iwate Medical University, School of Dentistry, Oral Anatomy II, Assistant Professor, 歯学部, 講師 (50057775)
FUJIWARA Naoki  Iwate Medical University, School of Dentistry, Oral Anatomy II, Assistant Professor, 歯学部, 講師 (20190100)
KAGIYA Tadayoshi  Iwate Medical University, School of Dentistry, Oral Anatomy II, Assistant Professor, 歯学部, 助手 (30405774)
Project Period (FY) 2004 – 2006
KeywordsFgf 10 / Fgf 9 / dental epithelial stem cells / mesenchymal stem cells / apical bud / stem cell niche / bioengineered teeth
Research Abstract

Mouse incisors are regenerative tissues, which grow continuously throughout life. We found that in the teeth, Fgf-9 plays a role of maintenance of mesenchymal cells expressing Fgf-10 and that the stem cell niche of incisors are formed by the epithelial-mesenchymal interaction via the signaling of Fgf-9 and Fgf-10. Immunostaining showed that Fgf-9 was expressed in the basal epithelium, stellate reticulum and inner enamel epithelium in the apical bud, and the expression area underlay the mesenchyme expressing Fgf-10. Recombinant Fgf-9 protein stimulated the increase of number of mesenchymal cells in a concentration-dependent manner. Annexin V staining and whole mount in situ hybridyzation using organ culture showed that recombinant Fgf-9 protein inhibited the apoptosis of mesenchymal cells of apical end and maintained the expression of Fgf-10. However, we could not success to produce bioengineered tooth germ and to culture these stem cells in the presence of only these factors.
Furthermore, we investigated the additionally factors in the culture medium and it was found that we needs FGF2 and EGF to culture the cells of the epithelial and mesenchymal stem cell compartment.
Finally, we succeeded to produce the regenerative bioengineered teeth using the dental epithelial stem cells and the mesenchymal stem cells of mouse incisors by the combination of collagen sponge and Fgf2/Egf/Fgf9/Fgf10-releasing gelatin beads. Now, we proceed to study the technical methods controlling the morphology and size of bioengineered tooth by these factors.

  • Research Products

    (42 results)

All 2007 2006 2005

All Journal Article (36 results) Book (6 results)

  • [Journal Article] The extended time to operate and the occlusal force influence determination of the pulpal healing pattern in replanted mouse molars.2007

    • Author(s)
      Hasegawa T., et al.
    • Journal Title

      Cell Tissue Res. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The extended time to operate and the occlusal force influence determination of the pulpal healing pattern in replanted mouse molars.2007

    • Author(s)
      Hasegawa T, Suzuki H, Yoshie H, Ohshima H
    • Journal Title

      Cell Tissue Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Stratum intermedium lineage diverges from ameloblast lineage via Notch signaling.2006

    • Author(s)
      Harada, H.
    • Journal Title

      Biochem. Biophys, Res. Commun. 340 (2)

      Pages: 611-616

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reuptake of extracellular amelogenin by dental epithelial cells results in increased levels of amelogenin mRNA through enhanced mRNA stabilization.2006

    • Author(s)
      Xu, L.
    • Journal Title

      J. Biol. Chem. 281 (4)

      Pages: 2257-2262

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] in vitro adipocytic conversion in Meckel's chondrocytes in response to a fatty acid-containing medium2006

    • Author(s)
      Ishizeki K., et al.
    • Journal Title

      Arch. Histl., Cytol. 69

      Pages: 163-171

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The exon 6ABC region of amelogenin mRNA contribute to increased levels of amelogenin mRNA through amelogenin protein-enhanced mRNA stabilization.2006

    • Author(s)
      Xu L., et al.
    • Journal Title

      J. Biol. Chem. 281 (43)

      Pages: 32439-32444

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth germs in a three-dimensional scaffold2006

    • Author(s)
      Iwatsuki S., et al.
    • Journal Title

      Eur. J. Oral Sci. 114

      Pages: 1-9

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Establishment of immortalized dental follicle cells for generating periodontal ligament in vivo.2006

    • Author(s)
      Yokoi T., et al.
    • Journal Title

      Cell Tissue Res. 327(Epub)

      Pages: 301-311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cessation of Fgf10 signaling, resulting in a defective dental epithelium stem cell ompartment, leads to the transition from crown to root formation.2006

    • Author(s)
      Yokohama-Tamaki T., et al.
    • Journal Title

      Development 133 (7)

      Pages: 1359-1366

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Histochemical and immunocytochemical study on hard tissue formation in dental pulp during the healing process after tooth replantation in rat molars.2006

    • Author(s)
      Tsukamoto-Tanaka H., et al.
    • Journal Title

      Cell Tissue Res. 325

      Pages: 219-229

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Capacity of dental pulp differentiation after tooth transplantation2006

    • Author(s)
      Ogawa R., et al.
    • Journal Title

      Cell Tissue Res. 326 (3)

      Pages: 715-724

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pulpal responses to cavity preparation in aged rat molars2006

    • Author(s)
      Kawagishi E., et al.
    • Journal Title

      Cell Tissue Res. 326

      Pages: 111-122

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The relationship between the termination of cell proliferation and expression of heat-shock protein-25 in the rat developing tooth germ.2006

    • Author(s)
      Nakasone N., et al.
    • Journal Title

      Eur. J. Oral Sci. 114(4)

      Pages: 302-309

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An immunohistochemical study of the expression of heat-shock protein-25 and cell proliferation in the dental pulp and enamel organ during odontogenesis in rat molars.2006

    • Author(s)
      Nakasone N., et al.
    • Journal Title

      Arch. Oral Biol. 51(5)

      Pages: 378-386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Odontoblast responses to GaAIAs laser irradiation in rat molars : an experimental study using heat-shock protein-25-immunohistochemistry.2006

    • Author(s)
      Tate Y., et al.
    • Journal Title

      Eur. J. Oral Sci. 114(1)

      Pages: 50-57

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Stratum intermedium lineage diverges from ameloblast lineage via Notch signaling.2006

    • Author(s)
      Harada H., Ichimori Y., Yokohama-Tamaki T., Ohshima H., Kawano S., Katsube K., Wakisaka S.
    • Journal Title

      Biochem. Biophys. Res. Commun. 340(2)

      Pages: 611-616

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reuptake of extracellular amelogenin by dental epithelial cells results in increased levels of amelogenin mRNA through enhanced mRNA stabilization.2006

    • Author(s)
      Xu L., Harada H., Yokohama-Tamaki T., Matsumoto S., Tanaka J., Taniguchi A.
    • Journal Title

      J. Biol. Chem. 281(4)

      Pages: 2257-2262

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] in vitro adipocytic conversion in Meckel's chondrocytes in response to a fatty acid-containing medium.2006

    • Author(s)
      Ishizeki, K., Kagiya T., Fujiwara N., Harada H.
    • Journal Title

      Arch. Histol., Cytol. 69

      Pages: 163-171

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The exon 6ABC region of amelogenin mRNA contribute to increased levels of amelogenin mRNA through amelogenin Protein-enhanced mRNA stabilization.2006

    • Author(s)
      Xu L., Harada H., Taniguchi A.
    • Journal Title

      J. Biol. Chem. 281(43)

      Pages: 32439-32444

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cell proliferation in teeth reconstructed fromdispersed cells of embryonic tooth germs in a three-dimensional scaffold.2006

    • Author(s)
      Iwatsuki S, Honda MJ, Harada H, Ueda M
    • Journal Title

      Eur. J. Oral Sci. 114

      Pages: 1-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment of immortalized dental follicle cells for generating periodontal ligament in vivo.2006

    • Author(s)
      Yokoi T., Saito M., Kiyono T., Iseki S., kosaka K., Nishida E., Tsubakimoto T., Harada H., Eto K., Noguchi T., Teranaka, T.
    • Journal Title

      Cell Tissue Res. 327(Epub)

      Pages: 301-311

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cessation of FgflO signaling, resulting in a defective dental epithelium stem cell compartment, leads to the transition from crown to root formation.2006

    • Author(s)
      Yokohama-Tamaki T, Ohshima H, Fujiwara N, Takada Y, Ichimori Y, Wakisaka S, Ohuchi H, Harada H.
    • Journal Title

      Development 133(7)

      Pages: 1359-1366

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Histochemical and immunocytochemical study on hard tissue formation in dental pulp during the healing process after tooth replantation in rat molars.2006

    • Author(s)
      Tsukamoto-Tanaka H., Ikegame M., Takagi R., Harada H., Ohshima H.
    • Journal Title

      Cell Tissue Res. 325(2)

      Pages: 219-229

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Capacity of dental pulp differentiation after tooth transplantation.2006

    • Author(s)
      Ogawa R., Saito C., Jung HS., Ohshima H.
    • Journal Title

      Cell Tissue Res. 326(3)

      Pages: 715-724

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pulpal responses to cavity preparation in aged rat molars.2006

    • Author(s)
      Kawagishi E., Nakakura-Ohshima K., Nomura S., Ohshima H.
    • Journal Title

      Cell Tissue Res. 326(1)

      Pages: 111-122

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The relationship between the termination of cell proliferation and expression of heat-shock protein-25 in the rat developing tooth germ.2006

    • Author(s)
      Nakasone N., Yoshie H., Ohshima H.
    • Journal Title

      Eur. J. Oral Sci. 114(4)

      Pages: 302-309

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An immunohistochemical study of the expression of heat-shock protein-25 and cell proliferation in the dental pulp and enamel organ during odontogenesis in rat molars.2006

    • Author(s)
      Nakasone N., Yoshie H., Ohshima H.
    • Journal Title

      Arch. Oral Biol. 51(5)

      Pages: 378-386

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Odontoblast responses to GaAIAs laser irradiation in rat molars : an experimental study using heat-shock proten-25-immunohistochemistry.2006

    • Author(s)
      Tate Y., Yoshiba K., Yoshiba N., Iwaku M., Okiji T., Ohshima H.
    • Journal Title

      Eur. J. Oral Sci. 114(1)

      Pages: 50-57

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In vitro differentiation of dental epithelial progenitor cells through epithelial-mesenchymal interactions.2005

    • Author(s)
      Morotomi, T., et al.
    • Journal Title

      Arch. Oral Biol. 50号

      Pages: 695-705

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The eternal tooth germ is formed at the apical end of continuously growing teeth.2005

    • Author(s)
      Ohshima, H., et al.
    • Journal Title

      Arch. Oral Biol. 50

      Pages: 153-157

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immortalization of cementoblast progenitor cells with Bmi-1 and TERT.2005

    • Author(s)
      Saito, M.
    • Journal Title

      J. Bone. Mineral. Res. 20(1)

      Pages: 50-57

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cell dynamics in the growth and differentiation of dental epithelium during tooth development : the lineage of stratum intermedium.2005

    • Author(s)
      Harada, H.
    • Journal Title

      J. Hard Tissue Biol. 14

      Pages: 172-173

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vitro differentiation of dental epithelial progenitor cells through enithelial-mesenchymal interactions.2005

    • Author(s)
      Morotomi T., Kawano S., Toyono T., Kitamura C., Terashita M., Uchida T., Toyoshima K., Harada H.
    • Journal Title

      Arch. Oral Biol. 50

      Pages: 695-705

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The eternal tooth germ is formed at the apical end of continuously growing teeth.2005

    • Author(s)
      Ohshima H., Nakasone N., Hashimoto E., Sakai H., Nakakura-Ohshima K., Harada H.
    • Journal Title

      Arch. Oral Biol. 50

      Pages: 153-157

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. (Epub 2004 Oct 18)2005

    • Author(s)
      Saito M., Handa K., Kiyono T., Hattori S., Yokoi T., Tsubakimoto T., Harada H., Noguchi T., Toyoda M., Sato S., Teranaka S.
    • Journal Title

      J. Bone Mineral. Res. 20(1)

      Pages: 50-7

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cell dynamics in the growth and differentiation of dental epithelium during tooth development : the lineage of stratum intermedium.2005

    • Author(s)
      Harada H.
    • Journal Title

      J. Hard Tissue Biol., 14

      Pages: 172-173

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 歯の再生 : 歯の発生生物学から歯の再生研究まで(歯の再生,上田実 本田雅規 編)(歯胚上皮系細胞)2006

    • Author(s)
      原田英光
    • Total Pages
      271
    • Publisher
      真興交易(株)医書出版部
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 歯の再生 : 歯の発生生物学から歯の再生研究まで(上田 実監修,本田雅規編著)(歯髄細胞の特性と分化能)(第2章 歯にかかわる細胞)2006

    • Author(s)
      大島勇人
    • Total Pages
      271
    • Publisher
      真興交易(株)医書出版部
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Dental epithelium in tooth germ.(Tooth regeneration)(eds. Ueda M., Masaki H.)2006

    • Author(s)
      Harada H.
    • Total Pages
      271
    • Publisher
      Shinkokoeki
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Characterization and Differentiation of Dental pulp cells(Tooth regeneration)(eds. Ueda M., Masaki H.)2006

    • Author(s)
      Ohshima H.
    • Total Pages
      271
    • Publisher
      Shinkokoeki
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Development and regeneration of oral tissue and organ(Frontier of Dental Science)(eds Hamada S., Yoneda S.)2006

    • Author(s)
      Harada H., Wakisaka S.
    • Total Pages
      273
    • Publisher
      Osaka University Publishers
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 先端歯科医学の創生(口腔諸器官の発生と再生)(浜田茂幸 米田俊之編)2005

    • Author(s)
      原田英光, 脇坂聡
    • Total Pages
      273
    • Publisher
      大阪大学出版会
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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