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Development of a method to prevent osteonecrosis of the jaw using organoids derived from dental pulp stem cells

Research Project

Project/Area Number 20K09997
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionKeio University

Principal Investigator

Yasui Takazumi  慶應義塾大学, 医学部(信濃町), 講師(非常勤) (80348771)

Co-Investigator(Kenkyū-buntansha) 中川 種昭  慶應義塾大学, 医学部(信濃町), 教授 (00227745)
森川 暁  慶應義塾大学, 医学部(信濃町), 講師 (00424169)
馬渕 洋  藤田医科大学, 医学部, 准教授 (50424172)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords歯髄幹細胞 / 顎骨壊死 / フローサイトメトリー / オルガノイド
Outline of Research at the Start

本研究では、ビスフォスフォネート製剤投与後の免疫不全マウスの抜歯窩に歯髄幹細胞由来オルガノイドを移植し、顎骨壊死予防への有用性について評価する。様々な原因が複合して発症していると思われるビスフォスフォネート関連顎骨壊死の予防について、骨形成および骨リモデリングの改善、血管新生、細菌暴露に対するバリアとしての軟組織の再生、抗炎症効果等の多方面から再生医療の有効性を評価する。

Outline of Final Research Achievements

We evaluated the usefulness of 3D cultured human dental pulp stem cells (3D hDPSCs) in preventing osteonecrosis of the jaw by transplanting them into the tooth extraction sockets of immunodeficient mice. Transplantation of 2D cultured human dental pulp stem cells (2D hDPSCs) was unable to prevent osteonecrosis of the jaw, but transplantation of 3D hDPSCs covered the tooth extraction socket with epithelium and no bone exposure was observed. Compared to the group transplanted with 2D hDPSCs, the group transplanted with 3D hDPSCs showed bone formation and the rate of empty lacunae was significantly lower. In addition, it was confirmed that 3D hDPSCs expressed high levels of FGF2. These results suggest that FGF2 expressed in 3D hDPSCs contributes to the prevention of osteonecrosis of the jaw.

Academic Significance and Societal Importance of the Research Achievements

薬剤関連顎骨壊死(MRONJ)は、ゾレドロン酸やデノスマブといった骨吸収抑制薬等により生じる顎骨壊死である。MRONJは一般に保存療法では治癒までに期間を要することが多く、外科療法では手術侵襲を伴う。そのために予防が重要となるが、抜歯により発症するリスクが高いため、抜歯時の予防手段を構築する必要がある。本研究では、抜歯時のMRONJ予防における3次元培養した歯髄幹細胞移植の有効性を示す社会的意義のある研究であると考えられた。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2023 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Treatment outcomes and time to healing of medication-related osteonecrosis of the jaw based on image findings2023

    • Author(s)
      Yasui Takazumi、Nagamine Hiroki、Tanaka Kenta、Kimura Moemi、Karube Takeshi、Kawana Hiromasa、Onizawa Katsuhiro
    • Journal Title

      Dentomaxillofacial Radiology

      Volume: 52 Issue: 5 Pages: 3203-3211

    • DOI

      10.1259/dmfr.20220352

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of prostate cancer status on the prevalence of medication-related osteonecrosis of the jaw2021

    • Author(s)
      Takazumi Yasui, Moemi Kimura, Hiroki Nagamine, Shosuke Yajima, Takeshi Karube, Hitoshi Sato, Seiji Asoda, Satoshi Hara, Katsuhiro Onizawa
    • Journal Title

      Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

      Volume: 131 Issue: 3 Pages: 312-318

    • DOI

      10.1016/j.oooo.2020.12.018

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2025-01-30  

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