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Development of primary repair of anterior cruciate ligament injury using induced regenerative medicine

Research Project

Project/Area Number 18K09091
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionHirosaki University

Principal Investigator

Ishibashi Yasuyuki  弘前大学, 医学研究科, 教授 (80292142)

Co-Investigator(Kenkyū-buntansha) 津田 英一  弘前大学, 医学研究科, 教授 (00361014)
木村 由佳  弘前大学, 医学研究科, 講師 (40455746)
佐々木 英嗣  弘前大学, 医学研究科, 助教 (60587038)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords再生医療 / 膝関節 / 軟骨 / 靱帯 / 半月板 / 変形性関節症 / スポーツ医学 / 前十字靭帯 / 再生医療 スポーツ医学 膝関節 前十字靭帯 / 前十字靱帯 / 再生誘導 / 修復
Outline of Final Research Achievements

We investigated whether intra-articular tissue damage, which does not easily heal spontaneously, can be repaired using a regeneration induction technique. We created a mouse model with osteochondral defects and administered HMGB-1 (high mobility group box-1 protein) peptide or saline (control group). Although the cartilage defect was repaired with fibrous tissue in the control group, it was repaired with hyaline cartilage in the HMGB-1 group. In the parabiosis model with cartilage defects, it was demonstrated that the administration of HMGB1 facilitates transmigration of bone marrow mesenchymal stem cells into the cartilage defects through blood circulation. Currently, similar experiments for meniscus and anterior cruciate ligament injuries are ongoing. Based on these results, we have started a physician-led clinical trial to evaluate the safety of HMGB1 administration for osteoarthritis of the knee.

Academic Significance and Societal Importance of the Research Achievements

HMGB-1(high mobility group box-1 protein)は核内遺伝子発現調節タンパクであり、重度の生体組織損傷時に血中に放出され骨髄由来間葉系幹細胞を血中へ動員する。しかし同時に全身性炎症も惹起するため、既知の炎症関連ドメインを排除したshort length HMGB-1 peptideを共同研究者の玉井らが開発した。今回の動物実験からその関節軟骨治癒促進効果が確認され、現在、変形性膝関節症に対する医師主導治験を開始している。HMGB-1が実用化されれば、本邦で2500万人といわれる変形性膝関節症患者のdisease modifying drugとなる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition2021

    • Author(s)
      Sasaki E, Chiba D, Ota S, Kimura Y, Sasaki S, Yamamoto Y, Oishi M, Iino K, Ando M, Tsuda E, Ishibashi Y.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 4931-4931

    • DOI

      10.1038/s41598-021-84584-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population2020

    • Author(s)
      Ishibashi Kyota、Sasaki Eiji、Ota Seiya、Chiba Daisuke、Yamamoto Yuji、Tsuda Eiichi、Yoshikuni Sugimura、Ihara Kazushige、Ishibashi Yasuyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 12310-12310

    • DOI

      10.1038/s41598-020-69328-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese Orthopaedic Association 2019 guidelines for anterior cruciate ligament injuries (3rd edition)2020

    • Author(s)
      Ishibashi Y Adachi NKoga HKondo EKuroda RMae TUchio Y
    • Journal Title

      J Orthop Sci

      Volume: 25(1) Issue: 1 Pages: 6-45

    • DOI

      10.1016/j.jos.2019.10.009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of the tibial tunnel position on knee joint stability and meniscal contact pressure after double-bundle anterior cruciate ligament reconstruction2020

    • Author(s)
      Sakamoto YTsukada HSasaki SYamamoto YTsuda EIshibashi Y
    • Journal Title

      J Orthop Sci

      Volume: - Issue: 6 Pages: 1040-1046

    • DOI

      10.1016/j.jos.2019.12.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patellofemoral contact pressure for medial patellofemoral ligament reconstruction using suture tape varies with the knee flexion angle: a biomechanical evaluation2020

    • Author(s)
      Sakamoto YSasaki SKimura YYamamoto YTsuda EIshibashi Y
    • Journal Title

      Arthroscopy

      Volume: - Issue: 5 Pages: 1390-1395

    • DOI

      10.1016/j.arthro.2019.12.027

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 単一細胞網羅的遺伝子発現解析に供するマウス軟骨細胞の単離方法の検討2021

    • Author(s)
      石橋 恭太、新保 敬史、佐々木 英嗣、宮下 和也、北山 智美、對馬 誉大、石橋 恭之、玉井 克人
    • Organizer
      日本整形外科基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 再生誘導医薬HMGB1ペプチドを利用した損傷軟骨治療の可能性2020

    • Author(s)
      石橋 恭太、佐々木 英嗣、對馬 誉大、新保 敬史、石橋 恭之玉井 克人
    • Organizer
      日本再生医療学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 内視鏡手術技術認定における医療安全 膝関節鏡技術認定制度における医療安全2019

    • Author(s)
      石橋恭之
    • Organizer
      日本整形外科学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 術中ナビゲーションによるACL遺残組織の生体力学的検討2019

    • Author(s)
      石橋恭之
    • Organizer
      JOSKAS
    • Related Report
      2019 Research-status Report
  • [Presentation] 膝関節鏡視下手術の進歩と現状2019

    • Author(s)
      石橋恭之
    • Organizer
      日本内視鏡外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児膝前十字靭帯損傷の手術待機期間と半月板損傷の関連2019

    • Author(s)
      木村由佳
    • Organizer
      JOSKAS
    • Related Report
      2019 Research-status Report
  • [Presentation] ACL単独再建術における再断裂について2019

    • Author(s)
      木村由佳
    • Organizer
      東日本整形外科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Graft choice in ACLR2019

    • Author(s)
      Ishibashi Y
    • Organizer
      2019 APKASS Summit Lancheon Sminar
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Return to Play after Revision ACL: Asia Experience2019

    • Author(s)
      Ishibashi Y
    • Organizer
      The ACL Consensus Meeting Panther Symposium 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 前十字靱帯(ACL)損傷診療ガイドライン 2019(改訂第3版)2019

    • Author(s)
      日本整形外科学会(石橋恭之他)編集
    • Total Pages
      85
    • Publisher
      南江堂
    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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