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Functional analysis of exosomes derived from stem cells from human exfoliated deciduous teeth and application to guiding bone regeneration in the jaw cleft

Research Project

Project/Area Number 21K10186
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionHiroshima University

Principal Investigator

Tanimoto Kotato  広島大学, 医系科学研究科(歯), 教授 (20322240)

Co-Investigator(Kenkyū-buntansha) 吉子 裕二  広島大学, 医系科学研究科(歯), 教授 (20263709)
加藤 功一  広島大学, 医系科学研究科(歯), 教授 (50283875)
國松 亮  広島大学, 医系科学研究科(歯), 准教授 (40580915)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエクソソーム / 再生医療 / 乳歯歯髄由来幹細胞 / 歯科矯正学
Outline of Research at the Start

本研究は、乳歯歯髄由来未分化間葉系幹細胞(SHED)から産生されるエクソソーム(SHED-Ex)の骨誘導能を明らかにするとともに、臨床的には口唇裂・口蓋裂(CL/P)における顎裂部の骨再生医療に応用することを目的とする。そのために、SHED-Exに内包されているmiRNAを解析し、再生部位における細胞の増殖や分化に対するSHED-Exの役割を明らかにする。さらに、未焼結炭酸アパタイト(CAP)担体にSHED-Exを含有させ、骨欠損部に移植することにより、矯正的な歯の移動が可能なCL/P顎裂閉鎖に最適化した骨再生誘導法を確立する。

Outline of Final Research Achievements

SHED is classified into several types based on surface antigens, among them, CD146-positive cells are suggested to promote angiogenesis in regenerated tissue through interaction with vascular endothelial cells, and are suggested to play an important role in bone regeneration. The particle size of the obtained SHED-derived exosome was 60-90 nm, and it was revealed that adding it to the culture medium enhanced the calcification ability of bone marrow-derived mesenchymal stem cells (BMSCs). It was also suggested that this effect is mediated by the MAPK pathway. Although DPSCs-derived exosome tended to enhance the calcification ability of BMSCs as well as SHED-derived exosome, no significant difference was observed between DPSCs- and SHED- derived exosomes.

Academic Significance and Societal Importance of the Research Achievements

本研究により、乳歯歯髄由来未分化間葉系幹細胞(SHED)から産生されるエクソソームが分離され、骨髄由来未分化間葉幹細胞に対する骨誘導能が明らかとなった。口唇裂・口蓋裂における顎裂部の骨再生医療へのSHED由来エクソソームの臨床応用の可能性が示されたことは、骨移植などの現行治療に比較して低侵襲の治療の達成につながることから、社会的意義があると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (15 results)

All 2024 2023 2022 2021

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Stem cells derived from human exfoliated deciduous teeth-based media in a rat root resorption model2024

    • Author(s)
      Odo Ayaka、Kunimatsu Ryo、Abe Takaharu、Sakata Shuzo、Nakatani Ayaka、Rikitake Kodai、Koizumi Yuma、Tanabe Izumi、Okimura Naonobu、Yoshimi Yuki、Tanimoto Kotaro
    • Journal Title

      Archives of Oral Biology

      Volume: 158 Pages: 105854-105854

    • DOI

      10.1016/j.archoralbio.2023.105854

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone Differentiation Ability of CD146-Positive Stem Cells from Human Exfoliated Deciduous Teeth2023

    • Author(s)
      Kunimatsu Ryo、Rikitake Kodai、Yoshimi Yuki、Putranti Nurul Aisyah Rizky、Hayashi Yoko、Tanimoto Kotaro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 4 Pages: 4048-4048

    • DOI

      10.3390/ijms24044048

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of carbonate apatite and stem cells from human deciduous teeth promotes bone regeneration by enhancing BMP2, VEGF, and CD31 expression in immunodeficient mice2022

    • Author(s)
      Putranti NAR., Rikitake K., Hiraki T., Nakajima K., Abe T., Tsuka Y., Sakata S., Nakatani A., Nikawa H., Tanimoto K.
    • Journal Title

      Cells

      Volume: 11(12) Issue: 12 Pages: 1914-1914

    • DOI

      10.3390/cells11121914

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Human Deciduous Dental Pulp-Derived Mesenchymal Stem Cell-Derived Conditioned Medium on the Metabolism of HUVECs, Osteoblasts, and BMSCs2022

    • Author(s)
      Kunimatsu R., Hiraki T., Rikitake K., Nakajima K., Putranti NAR., Abe T., Ando K., Nakatani A., Sakata S., Tanimoto K.
    • Journal Title

      Cells

      Volume: 11(20) Issue: 20 Pages: 3222-3222

    • DOI

      10.3390/cells11203222

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Study of Alveolar Bone Remodeling Using Deciduous Tooth Stem Cells and Hydroxyapatite by Vascular Endothelial Growth Factor Enhancement and Inhibition of Matrix Metalloproteinase-8 Expression in vivo2022

    • Author(s)
      Saskianti Tania、Nugraha Alexander Patera、Prahasanti Chiquita、Ernawati Diah Savitri、Tanimoto Kotaro、Riawan Wibi、Kanawa Masami、Kawamoto Takeshi、Fujimoto Katsumi
    • Journal Title

      Clinical, Cosmetic and Investigational Dentistry

      Volume: Volume 14 Pages: 71-78

    • DOI

      10.2147/ccide.s354153

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of CD146+ SHED on bone regeneration in a mouse calvaria defect model2021

    • Author(s)
      Rikitake K., Kunimatsu R., Yoshimi Y., Nakajima K., Hiraki T., Putranti NA., Tsuka Y., Abe T., Ando K., Hayashi Y., Nikawa H., Tanimoto K
    • Journal Title

      Oral Dis

      Volume: - Issue: 2 Pages: 725-734

    • DOI

      10.1111/odi.14020

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 乳歯歯髄由来間葉系幹細胞および炭酸アパタイト担体を用いた顎裂閉鎖を目指した基礎的研究2023

    • Author(s)
      國松 亮,力武航大,吉見友希,阿部崇晴,谷本幸太郎
    • Organizer
      第47回日本口蓋裂学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] CD146 陽性乳歯歯髄由来間葉系幹細胞の骨分化能についての検討2023

    • Author(s)
      力武航大, 國松亮, 吉見友希, 阿部崇晴, 谷本幸太郎
    • Organizer
      第47回日本口蓋裂学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト乳歯由来歯髄間葉系幹細胞の培養上清が骨芽細胞および骨髄由来間葉系幹細胞の代謝に及ぼす影響2023

    • Author(s)
      國松亮,平木智香,力武航大,坂田修三,阿部崇晴,安藤和代,中谷文香,谷本幸太郎
    • Organizer
      第82回日本矯正歯科学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] CD146 陽性乳歯歯髄由来間葉系幹細胞を用いた骨再生治療への応用2022

    • Author(s)
      力武航大, 國松亮, 吉見友希, 中島健吾, 平木智香, Putranti NAR., 柄 優至, 阿部崇晴, 安藤和代, 谷本幸太郎
    • Organizer
      第46回日本口蓋裂学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] CD146 陽性乳歯歯髄由来間葉系幹細胞の骨分化能についての評価2022

    • Author(s)
      力武航大, 國松 亮, 吉見友希, 中島健吾, 平木智香, Putranti NAR., 柄 優至, 阿部崇晴, 安藤和代, 谷本幸太郎
    • Organizer
      第81回日本矯正歯科学会学術大会&第9回日韓ジョイントシンポジウム
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳歯歯髄由来間葉系幹細胞および炭酸アパタイト担体を併用した骨再生治療への応用2022

    • Author(s)
      Putranti NAR., 國松 亮, 力武航大, 平木智香, 吉見友希, 中島健吾, 柄 優至, 阿部崇晴, 坂田修三, 中谷文香, 二川浩樹, 谷本幸太郎
    • Organizer
      第81回日本矯正歯科学会学術大会&第9回日韓ジョイントシンポジウム
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 歯髄由来間葉系幹細胞のエクソソームが骨髄由来間葉系幹細胞に及ぼす影響2022

    • Author(s)
      阿部崇晴, 國松亮, 伊藤翔太, 坂田修三, 力武航大, Putranti NAR., 柴田梨央, 谷本幸太郎
    • Organizer
      第61回広島県歯科医学会・第106回広島大学歯学会例会
    • Related Report
      2022 Research-status Report
  • [Presentation] 乳歯歯髄由来間葉系幹細胞および炭酸アパタイト担体を併用した骨再生治療への応用2022

    • Author(s)
      Putranti NAR., 國松 亮, 力武航大, 平木智香, 吉見友希, 中島健吾, 柄 優至, 阿部崇晴, 坂田修三, 中谷文香, 二川浩樹, 谷本幸太郎
    • Organizer
      第61回広島県歯科医学会・第106回広島大学歯学会例会
    • Related Report
      2022 Research-status Report
  • [Presentation] CD146陽性乳歯歯髄由来間葉系幹細胞を用いた骨再生治療への応用2021

    • Author(s)
      力武航大, 國松亮, 吉見友希, 中島健吾, 平木智香, Putranti NAR., 柄優至, 阿部崇晴, 安藤和代, 林陽子, 二川浩樹, 谷本幸太郎
    • Organizer
      第80回日本矯正歯科学会大会・第5回国際会議
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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