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Development of the new periodontal ligament regeneration method based on iPS-derived neural crest cells

Research Project

Project/Area Number 17H04385
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Conservative dentistry
Research InstitutionKyushu University

Principal Investigator

Tomokiyo Atsushi  九州大学, 大学病院, 講師 (20507777)

Co-Investigator(Kenkyū-buntansha) 前田 英史  九州大学, 歯学研究院, 教授 (10284514)
吉田 晋一郎  九州大学, 大学病院, 助教 (30778866)
濱野 さゆり  九州大学, 歯学研究院, 助教 (40757978)
和田 尚久  九州大学, 大学病院, 教授 (60380466)
杉井 英樹  九州大学, 歯学研究院, 助教 (80802280)
長谷川 大学  九州大学, 大学病院, 助教 (20757992)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords生体模倣 / 歯根膜幹細胞 / 神経堤細胞 / iPS細胞 / 低分子量ヒアルロン酸 / 歯周組織再生療法 / ヒアルロン酸 / 歯周組織再生 / バイオミメティクス / マイクロアレイ / ティッシュエンジニアリング / 低分子化合物 / 歯根膜 / 再生 / Wntシグナル / 歯周病 / バイオミメティクス技術 / 幹細胞 / 細胞移植 / 歯根膜再生 / 再生医療への応用 / マイクロアレイ解析 / 人工多能性幹細胞(iPSC) / 歯周組織
Outline of Final Research Achievements

Our microarray analysis demonstrated that CD44 expression was up-regulated during iPS-PDLSC differentiation. CD44 is known as a kind of HA receptor, therefore we hypothesis that HA should play important roles in the differentiation of iPS-NC into iPS-PDLSC. A human NC cell line cultured with HA increased PDLSC-related genes, such as COL-1, FBN1, OPG, and POSTN, compared with cells cultured without HA. Our result suggested that HA would promote the differentiation of iPS-NC into iPS-PDLSC.

Academic Significance and Societal Importance of the Research Achievements

現在用いられている歯周組織再生療法は、タンパク製剤を用いる方法であり、組織再生に必要な3要素のうち、シグナル因子のみを活用する方法である。申請者らが開発を目指す歯周組織再生療法は、iPS細胞由来神経堤細胞(iPS-NC)および低分子量ヒアルロン酸(LHA)を用いて、歯周組織の発生模倣を基盤とし、歯周組織再生を実現させようとするものである。LHAの働きにより、神経堤細胞様細胞が歯根膜幹細胞様細胞へと分化誘導されることが明らかとなった。この成果は、iPS-NCをLHAを基盤とする足場材と共に移植する方法が、新たな歯周組織再生療法となりうる可能性を示唆しており、非常に意義の高いものである。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (14 results) (of which Int'l Joint Research: 5 results) Book (2 results)

  • [Journal Article] Generation of biohybrid implants using a multipotent human periodontal ligament cell line and bioactive core materials.2021

    • Author(s)
      Ono T, Tomokiyo A, Ipposhi K, Yamashita K, Alhasan MA, Miyazaki Y, Kunitomi Y, Tsuchiya A, Ishikawa K, Maeda H.
    • Journal Title

      J Cell Physiol.

      Volume: - Issue: 9 Pages: 30336-30336

    • DOI

      10.1002/jcp.30336

    • NAID

      120007193918

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells2020

    • Author(s)
      Daigaku Hasegawa, Kana Hasegawa, Hiroshi Kaneko, Shinichiro Yoshida, Hiromi Mitarai, Mai Arima, Atsushi Tomokiyo, Sayuri Hamano, Hideki Sugii, Naohisa Wada, Tamotsu Kiyoshima, Hidefumi Maeda
    • Journal Title

      Stem Cells International

      Volume: - Pages: 1-15

    • DOI

      10.1155/2020/9672673

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy.2020

    • Author(s)
      Yoshida S, Tomokiyo A, Hasegawa D, Hamano S, Sugii H, Maeda H.
    • Journal Title

      Biology-Basel.

      Volume: 9 Issue: 7 Pages: 160-160

    • DOI

      10.3390/biology9070160

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible function of GDNF and Schwann cells in wound healing of periodontal tissue.2020

    • Author(s)
      Itoyama T, Yoshida S, Tomokiyo A, Hasegawa D, Hamano S, Sugii H, Ono T, Fujino S, Maeda H.
    • Journal Title

      J Periodont Res.

      Volume: 55 Issue: 6 Pages: 830-839

    • DOI

      10.1111/jre.12774

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functions of beta2‐adrenergic receptor in human periodontal ligament cells2020

    • Author(s)
      Hamano Sayuri、Tomokiyo Atsushi、Hasegawa Daigaku、Yuda Asuka、Sugii Hideki、Yoshida Shinichiro、Mitarai Hiromi、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Journal of Cellular Biochemistry

      Volume: 121 Issue: 12 Pages: 4798-4808

    • DOI

      10.1002/jcb.29706

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and function of dopamine in odontoblasts2019

    • Author(s)
      Fujino Shoko、Hamano Sayuri、Tomokiyo Atsushi、Itoyama Tomohiro、Hasegawa Daigaku、Sugii Hideki、Yoshida Shinichiro、Washio Ayako、Nozu Aoi、Ono Taiga、Wada Naohisa、Kitamura Chiaki、Maeda Hidefumi
    • Journal Title

      Journal of Cellular Physiology

      Volume: 235 Issue: 5 Pages: 4376-4387

    • DOI

      10.1002/jcp.29314

    • NAID

      120006892319

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Periodontal Ligament Stem Cells: Regenerative Potency in Periodontium2019

    • Author(s)
      Tomokiyo Atsushi、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Stem Cells and Development

      Volume: 28 Issue: 15 Pages: 974-985

    • DOI

      10.1089/scd.2019.0031

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] R-spondin 2 promotes osteoblastic differentiation of immature human periodontal ligament cells through the Wnt/β-catenin signaling pathway2018

    • Author(s)
      Arima Mai、Hasegawa Daigaku、Yoshida Shinichiro、Mitarai Hiromi、Tomokiyo Atsushi、Hamano Sayuri、Sugii Hideki、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Journal of Periodontal Research

      Volume: 54 Issue: 2 Pages: 143-153

    • DOI

      10.1111/jre.12611

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection, Characterization, and Clinical Application of Mesenchymal Stem Cells in Periodontal Ligament Tissue.2018

    • Author(s)
      Tomokiyo A, Yoshida S, Hamano S, Hasegawa D, Sugii H, Maeda H.
    • Journal Title

      Stem Cells Int.

      Volume: 26 Pages: 1-9

    • DOI

      10.1155/2018/5450768

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells2018

    • Author(s)
      Hamano Sayuri、Tomokiyo Atsushi、Hasegawa Daigaku、Yoshida Shinichiro、Sugii Hideki、Mitarai Hiromi、Fujino Shoko、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Stem Cells and Development

      Volume: 27 Issue: 2 Pages: 100-111

    • DOI

      10.1089/scd.2017.0077

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] sFRP1は歯髄細胞の象牙芽細胞様分化を誘導し、デンティンブリッジ形成を促進する2020

    • Author(s)
      一法師 啓太、友清 淳、小野 太雅、山下梢、長谷川 大学、濱野 さゆり、吉田 晋一郎、杉井 英樹、前田 英史
    • Organizer
      第41回日本歯内療法学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] フェノール系貼薬剤は硬化後のWhite Mineral Trioxide Aggregateの崩壊および色調変化を誘導する2020

    • Author(s)
      友清 淳、山下 梢、小野 太雅、一法師 啓太、濱野 さゆり、長谷川 大学、杉井 英樹、吉田 晋一郎、前田 英史.
    • Organizer
      第41回日本歯内療法学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Develpoment of a new biohybridimplant system applying 3D-printing technology2020

    • Author(s)
      T. Ono, A. Tomokiyo, D. Hasegawa, S. Hamano, S. Yoshida, H. Sugii, S. Fujino, T. Itoyama, H. Maeda.
    • Organizer
      The 98th General Session & Exhibition of the IADR
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Possibility of Schwann cells to contribute to periodontal wound healing2020

    • Author(s)
      T. Itoyama, S. Yoshida, A. Tomokiyo, D. Hasegawa, S. Hamano1, H. Sugii, T. Ono, S. Fujino, H. Maeda
    • Organizer
      The 98th General Session & Exhibition of the IADR
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レジン系、バイオガラス系およびシリコン系根管充填用シーラーのヒト歯根膜幹細胞株に対する細胞親和性比較2020

    • Author(s)
      友清 淳、長谷川 大学、小野 太雅、一法師 啓太、山下 梢、M Anas Alhasan、濱野さゆり、杉井 英樹、吉田 晋一郎、前田 英史.
    • Organizer
      第152回日本歯科保存学会春季学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of TNF-a. on Senescent human dental pulp cells.2019

    • Author(s)
      Aoi Nozu, Sayuri Hamano ,Atsushi Tomokiyo, Daigaku Hasegawa, Shinichiro Yoshida, Hideki Sugii,Hiromi Mitarai, Keita Ipposhi, Naohisa Wada, Hidefumi Maeda.
    • Organizer
      Kyudai Oral Bioscience&OBT Research Center Joint International Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of dopamine on odontoblastic differentiation through PKA signaling2019

    • Author(s)
      Shoko Fujino, Hamano Sayuri, Atsushi Tomokiyo, Daigaku Hasegawa, Shinichiro Yoshida, Hideki Sugii, Ayako Washio, Hiromi Mitarai, Naohisa Wada, Chiaki Kitamura, Hidefumi Maeda.
    • Organizer
      The 97th General Session & Exhibition of the IADR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activin Aが有する二極性の細胞分化誘導能に関する分子機構の解明.2019

    • Author(s)
      杉井英樹、友清淳、濱野さゆり、長谷川大学、吉田晋一郎、Mhd Safwan Albougha、前田英史
    • Organizer
      日本歯科保存学会2019年度春季学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Discoloration of White Mineral Trioxide Aggregate Immersed in Various Solutions2018

    • Author(s)
      TOMOKIYO Atusushi, HAMANO Sayuri, HASEGAWA Daigaku, SUGII Hideki, YOSHIDA Shinichirou, MITARAI Hiromi, ARIMA Mai, NOZU Aoi, WADA Naohisa, MAEDA Hidefumi
    • Organizer
      International Association of Dental Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト歯根膜クローン細胞株およびハイドロキシアパタイト焼成体を用いた人工歯根作製についての検討2018

    • Author(s)
      小野太雅、友清淳、長谷川大学、濱野さゆり、吉田晋一郎、杉井英樹、有馬麻衣、野津葵、和田尚久、前田英史
    • Organizer
      第149回日本歯科保存学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Basic fibroblast growth factorおよびephrinB2がヒト歯根膜細胞の増殖に及ぼす影響について2018

    • Author(s)
      小野太雅、友清淳、長谷川大学、濱野さゆり、吉田晋一郎、杉井英樹、有馬麻衣、野津葵、和田尚久、前田英史
    • Organizer
      第148回日本歯科保存学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト歯髄細胞の象牙芽細胞分化に及ぼすsFRP1の影響について2018

    • Author(s)
      一法師啓太、友清淳、長谷川大学、濱野さゆり、吉田晋一郎、杉井英樹、有馬麻衣、野津葵、和田尚久、前田英史
    • Organizer
      第149回日本歯科保存学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] iPS細胞由来の歯根膜幹細胞様細胞の樹立2018

    • Author(s)
      濱野さゆり、友清淳、長谷川大学、杉井英樹、吉田晋一郎、御手洗裕美、有馬麻衣、野津葵、藤野翔香、和田尚久、前田英史
    • Organizer
      第17回再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞由来の歯根膜幹細胞様細胞の樹立2018

    • Author(s)
      濱野さゆり
    • Organizer
      OBT研究センター キックオフシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Book] Precision Medicine.2019

    • Author(s)
      友清 淳
    • Publisher
      北隆館
    • Related Report
      2019 Annual Research Report
  • [Book] BIO Clinica.2019

    • Author(s)
      友清 淳
    • Publisher
      北隆館
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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