Induction of differentiation of dental mesenchymal cells from human iPS cells

• Project/Area Number: 17K17304
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: Seki Daisuke 東北大学, 歯学研究科, 大学院非常勤講師 (90758442)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: iPS細胞 / 歯 / 再生医療 / 歯学

Outline of Final Research Achievements

To achieve regeneration of tooth, we need to develop novel culture method to generate enough cells with good quality. The aim of this study is to establish methods to differentiate dental mesenchymal cells from human iPS cells using transfection and spheroid culture. I succeeded to obtain neural crest cells derived from feeder-free-cultured human iPS cells. The human iPS cell-derived neural crest cells showed expression of neural crest marker genes. I further performed transfection and conditioned medium treatment to induce the development of dental mesenchymal cell from the human iPS cell-derived neural crest cells.

Academic Significance and Societal Importance of the Research Achievements

歯の再生は広く社会から切望されている。歯の再生を実現するには、幹細胞から歯を構成する上皮・間葉細胞への分化誘導方法を確立しなけらばならない。本研究により、ヒトiPS細胞から神経堤細胞を経て歯性間葉細胞の分化を誘導する技術を開発するための基盤的知見が得られた。これらの知見に基づき、今後さらにヒトへ応用可能な、安全で効率的なiPS細胞由来歯性細胞分化技術開発の進展が期待される。

Research Products

• [Journal Article] Improvement of Open Bite and Stomatognathic Function in an Axenfeld- Rieger Syndrome Patient by Orthodontic Sectional Arch Mechanics: Clinical Considerations and the Risk of Orthodontic Tooth Movement (2019)
  • Author(s): Daisuke Seki, Nobuo Takeshita, Masahiro Seiryu, Toru Deguchi, Teruko Takano-Yamamoto
  • Journal Title: Acta Medica Okayama Volume: 73 Issue: 3 Pages: 255-262
  • DOI: 10.18926/AMO/56869
  • NAID: 120006648005
  • URL: https://ousar.lib.okayama-u.ac.jp/56869
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis. (2019)
  • Author(s): Oyanagi T, Takeshita N, Hara M, Ikeda E, Chida T, Seki D, Yoshida M, Seiryu M, Takano I, Kimura S, Oshima M, Tsuji T, Takano-Yamamoto T
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 368-368
  • DOI: 10.1038/s41598-018-36863-6
  • NAID: 120006875661
  • Peer Reviewed / Open Access
• [Presentation] IGF1 regulates morphogenesis of bioengineered teeth via proliferation and differentiation of dental epithelial and mesenchymal cells (2018)
  • Author(s): Toshihito Oyanagi，Nobuo Takeshita，Mamiko Hara，Etsuko Ikeda， Toko Chida，Daisuke Seki，Michiko Yoshida，Masahiro Seiryu，Ikuko Takano，Seiji Kimura，Masamitsu Oshima，Takashi Tsuji，Teruko Takano-Yamamoto,
  • Organizer: 5th Tissue Engineering and Regenerative Medicine International Society World Congress, Kyoto, Japan
• [Presentation] Odz3はRhoA、アクチン制御を介した遊走促進および分化の促進により、ATDC5の軟骨細胞分化を調整する (2018)
  • Author(s): 高野郁子、竹下信郎、関大輔、大柳俊仁、吉田倫子、木村晴地、川津正慶、山本照子
  • Organizer: 第７７回日本矯正歯科学会大会、横浜
• [Presentation] 膜タンパク質Ten-m/Odz3はFGF2によるRhoA活性制御を介してATDC5のアクチン再構成、遊走、分化を促す (2018)
  • Author(s): 竹下信郎、高野郁子、関大輔、大柳俊仁、吉田倫子、山本照子
  • Organizer: 第３６回日本骨代謝学会学術集会、長崎