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Establishment of minimally invasive bone regeneration for cleft lip and palate using mesenchymal stem cell exosomes derived from deciduous dental pulp

Research Project

Project/Area Number 21K17186
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Abe Takaharu  広島大学, 病院(歯), 助教 (20806682)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエクソソーム / 培養上清 / SHED / DPSC / HCEM / 骨再生 / miRNA / SHED-CM
Outline of Research at the Start

本研究は、乳歯歯髄由来間葉系幹細胞培養上清(SHED-CM)に含まれる液性因子や細胞外の小胞エクソソーム (SHED-EXs) の、骨再生への関与について、骨再生機構を明らかとすること、SHED-EXs を応用した新規の顎裂部骨再生治療法の確立を目指すことを目的とする。
抽出したSHED-Exsについて、成分解析をするとともにヒト由来血管内皮細胞株 (HUVEC)およびマウス頭蓋冠由来骨芽細胞株 (MT3T3-E1)に対する影響を調査する。また、マウス頭蓋骨骨欠損部にSHED-Exsの移植を行うことで、三次元および組織学的に骨再生の評価を行う。

Outline of Final Research Achievements

Exosomes extracted from the culture supernatant of mesenchymal stem cells (MSCs) isolated and cultured from the dental pulp of deciduous teeth were called SHED-EXs, and exosomes isolated from the culture supernatant of MSCs isolated from the pulp of permanent teeth were called DPSC-EXs. It was used for. An increase in cell number was observed by adding SHED-Exo and DPSC-EXs to bone marrow-derived mesenchymal stem cells (BMSCs) and human osteoblasts (HCO). Furthermore, when SHED-EXs and DPSC-EXs were added to BMSCs and HCOs that had been induced to undergo osteogenic differentiation, and quantitative evaluation was performed using alizarin red staining, it was found that the addition of exosomes enhanced osteogenic differentiation.

Academic Significance and Societal Importance of the Research Achievements

脱落あるいは便宜的に抜去する乳歯あるいは永久歯より、採取される歯髄は、従来行われてきた腸骨より採取する骨髄を用いるよりも低侵襲である。また、その培養上清より抽出した、エクソソームの骨形成への関与について解明した点において、本研究の学術的意義は高い。miRNAおよび細胞増殖、ALPやMAPKを介して、骨形成を促進させることを明らかとした。今後さらに、エクソソームを臨床応用し患者の負担が軽減され、低侵襲で良好な骨再生療法を確立する、社会的観点から重要な意義がある。

Report

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

    (7 results)

All 2022 2021

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 1 results)

  • [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] 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] 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] 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
  • [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] Stem cell-based therapy for patients with cleft lip and palate2021

    • Author(s)
      Takaharu Abe
    • Organizer
      The 6th Join Scientific Meeting in Dentistry
    • Related Report
      2021 Research-status Report
    • Invited

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

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