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Periodontal tissue regenerative medicine through LAP-dependent tissue remodeling

Research Project

Project/Area Number 21H03118
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionOsaka University

Principal Investigator

Takedachi Masahide  大阪大学, 歯学部附属病院, 講師 (60452447)

Co-Investigator(Kenkyū-buntansha) 北村 正博  大阪大学, 大学院歯学研究科, 准教授 (10243247)
村上 伸也  大阪大学, 大学院歯学研究科, 教授 (70239490)
岩山 智明  大阪大学, 大学院歯学研究科, 助教 (80757865)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords歯周組織再生 / 脂肪組織由来多系統前駆細胞 / efferycytosis / efferocytosis / LAP
Outline of Research at the Start

研究では、歯周組織に移植した脂肪組織由来多系統前駆細胞(ADMPC)がアポトーシスする過程においてefferocytosisの実行細胞を同定し、efferocytosis実行後の細胞機能変化が歯周組織の再生に及ぼす影響、さらに同変化におけるLAPの役割についてin vitro、in vivoの両面から明らかにする。さらに、efferocytosisあるいはLAPの活性化がADMPC移植による歯周組織再生効果の増強につながることを明らかにする。

Outline of Final Research Achievements

In this study, we investigated the effects of allogeneic transplantation of adipose tissue-derived multilineage progenitor cells (ADMPC) on periodontal tissue regeneration, and the impact of apoptosis in transplanted cells and host apoptotic processing mechanisms on these effects. ADMPCs were transplanted into a rat periodontal tissue defect model, resulting in significant periodontal tissue regeneration. However, the transplanted ADMPCs underwent apoptosis within 14 days post-transplantation. It was found that the transplantation of apoptosis-resistant ADMPCs significantly reduced tissue regeneration effects compared to the control group. Furthermore, in vitro analysis revealed that the macrophages underwent efferocytosis of apoptosis-induced ADMPCs, which altered their phenotype to a reparative one.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、脂肪組織由来間葉系幹細胞の同種移植による歯周組織再生効果と、同効果における分子機序の一つとして細胞のアポトーシスおよび宿主によるefferocytosisの関与が明らかとなった。この結果は、間葉系幹細胞移植治療による抗炎症効果のみならず、組織再生に対しても宿主のアポトーシス細胞処理機構が重要であることを示唆するとともに、幹細胞移植による歯周組織再生療法の開発を推進するための基盤情報となる。

Report

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

    (8 results)

All 2024 2023 2022

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

  • [Journal Article] Elucidation of Periodontal Tissue Homeostatic Mechanisms and Development of Stem Cell Transplantation Therapy for Periodontal Tissue Regeneration2023

    • Author(s)
      Takedachi Masahide
    • Journal Title

      Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology)

      Volume: 65 Issue: 4 Pages: 109-116

    • DOI

      10.2329/perio.65.109

    • ISSN
      0385-0110, 1880-408X
    • Year and Date
      2023-12-28
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periodontal Tissue Regeneration by Transplantation of Autologous Adipose Tissue-Derived Multi-Lineage Progenitor Cells With Carbonate Apatite2023

    • Author(s)
      Takedachi Masahide、Kawasaki Kohsuke、Sawada Keigo、Sakura Kazuma、Murata Mari、Shimomura Junpei、Kawakami Kazuma、Morimoto Chiaki、Miki Koji、Takeshita Noboru、Iwayama Tomoaki、Okura Hanayuki、Matsuyama Akifumi、Saito Masahiro、Kitamura Masahiro、Murakami Shinya
    • Journal Title

      Cell Transplantation

      Volume: 32

    • DOI

      10.1177/09636897231198296

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of periodontal ligament cell cytodifferentiation by juxtacrine signaling from cementoblasts2023

    • Author(s)
      Sawada Keigo、Shimomura Junpei、Takedachi Masahide、Murata Mari、Morimoto Chiaki、Kawasaki Kohsuke、Kawakami Kazuma、Iwayama Tomoaki、Murakami Shinya
    • Journal Title

      Journal of Periodontology

      Volume: 95 Issue: 3 Pages: 256-267

    • DOI

      10.1002/jper.23-0211

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脂肪組織由来多系統前駆細胞を用いた歯周組織再生医療開発の現状と課題2024

    • Author(s)
      竹立匡秀
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Development of allogeneic stem cell therapy for periodontal tissue regeneration: analysis of cell fate after transplantation2023

    • Author(s)
      Takedachi M, Kawakami K, Kawasaki K, Sawada K, Murata M, Morimoto C, Sugimoto A, Iwayama T, Kitamura M, Murakami S.
    • Organizer
      第71回JADR総会・学術大会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂肪組織由来多系統前駆細胞の同種移植による歯周組織再生効果と移植細胞の動態解析2023

    • Author(s)
      河上和馬、竹立匡秀、森本千晶、川嵜公輔、村田真里、杉本彩、沢田啓吾、三木康史、岩山智明、村上伸也
    • Organizer
      第66回秋季日本歯周病学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周組織の理解の深化と幹細胞移植治療への応用2023

    • Author(s)
      竹立匡秀
    • Organizer
      第66回春季日本歯周病学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Carbonate apatite as a scaffold for periodontal regeneration cell therapy2022

    • Author(s)
      Kawasaki K、 Takedachi M、 Sawada K、 Morimoto C、 Hirai A、 Shimomura J、 Murata M、 Kawakami K、 Miki K、 Takeshita N、 Sakura K、 Matsuyama A、 Okura H、 Kitamura M、 Murakami S
    • Organizer
      100th General Session of the International Association for Dental Research
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research

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

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