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Basic research on cell therapy by macrophages aimed for periprosthetic joint infections

Research Project

Project/Area Number 22K09299
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Takagi Michiaki  山形大学, 医学部, 教授 (40241707)

Co-Investigator(Kenkyū-buntansha) 丸山 真博  山形大学, 医学部, 客員研究員 (00740870)
伊藤 重治  山形大学, 医学部, 客員研究員 (50764122)
本間 龍介  山形大学, 医学部, 非常勤講師 (70716688)
高窪 祐弥  山形大学, 医学部, 准教授 (80431641)
鈴木 智人  山形大学, 医学部, 助教 (90599416)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords人工関節周囲感染 / オートファジー / 炎症性滑膜組織 / マクロファージ / 組織修復 / 炎症性滑膜炎 / 滑膜炎 / ネトーシス / 自然免疫
Outline of Research at the Start

人工関節手術の普及、手術数の増加に伴い人工関節周囲感染(PJI)は臨床上解決すべき大きな課題となっている。特に難治化したPJIでは新たな視点から治療法の開発が望まれている。本申請研究では、これまでの研究で得られた知見をもとに、自然免疫系細胞、特にマクロファージの細胞機能に着目した細胞治療の基礎研究を発展的に推進する。

Outline of Final Research Achievements

To analyze biological host response in the inflammatory arthritis, including periprosthetic joint infection (PJI), and to promote cellular therapy for corresponding inflammation, tissues from inflammatory synovitis were examined, and phenotype of macrophages and the cellular function, including autophagy, were analyzed. In the process of inflammation, fibrotic change was observed and the key cell to promote anti-inflammatory and tissue-repairing was macrophages, which were subtyped as M0, M1, M2, and M1/M2. In addition, autophagy function was prominent in the macrophages expressing M1/M2 or M2, which seemed to contribute to anti-inflammation and tissue repairing. There potent phenotypes of macrophage could be applied to modulate inflammations in the joints, including PJI, as one of cell therapies.

Academic Significance and Societal Importance of the Research Achievements

PJIをはじめとする炎症性関節炎における滑膜炎では、M0, M1, M2, M1/M2の表現形質を有するマクロファージが存在し、特にM1/M2双方の形質を有するマクロファージがオートファジー機能を亢進させながら抗炎症・組織修復に働いている可能性を示した点に新規性がある。今後、細胞機能をさらに解析しながら、PJIを含む炎症性関節炎において抗炎症・組織修復性のマクロファージを用いた細胞治療の開発、応用が期待される。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (17 results)

All 2025 2024 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (1 results) Presentation (10 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results) Book (5 results)

  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials2023

    • Author(s)
      Gibon Emmanuel、Takakubo Yuya、Zwingenberger Stefan、Gallo Jiri、Takagi Michiaki、Goodman Stuart B.
    • Journal Title

      Journal of Biomedical Materials Research Part A

      Volume: 1 Issue: 8 Pages: 1-16

    • DOI

      10.1002/jbm.a.37599

    • Related Report
      2023 Research-status Report
  • [Presentation] Analysis of macrophage subtype in the synovium of rheumatoid arthritis2025

    • Author(s)
      Hanqing Huang, Yuya Takakubo, Masahiro Maruyama, Tomohiro Uno, Takeru Akabane, Takahiro Igarashi, Naomi Hanaka, Yunzhi Peter Yang, Stuart B. Goodman, Michiaki Takagi
    • Organizer
      Orthopaedics Research Society Annual Meeting
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of macrophage subtype in the synovium of rheumatoid arthritis2025

    • Author(s)
      Hanqing Huang, Yuya Takakubo, Takeru Akabane, Naomi Hanaka, Michiaki Takagi
    • Organizer
      Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
    • Related Report
      2024 Annual Research Report
  • [Presentation] Analysis on macrophage subtype alteration in the synovium of rheumatoid arthritis2024

    • Author(s)
      Hanqing Huang, Yuya Takakubo, Masahiro Maruyama, Tomohiro Uno, Takeru Akabane, Takahiro Igarashi, Xing Liu, Yunzhi Peter Yang, Stuart B. Goodman, Michiaki Takagi
    • Organizer
      Orthopaedics Research Society Annual Meeting
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis on macrophage subtype and autophagy expression in the cells derived from the synovium of rheumatoid arthritis2024

    • Author(s)
      Hanqing Huang, Yuya Takakubo, Masahiro Maruyama, Tomohiro Uno, Takeru Akabane, Takahiro Igarashi, Yunzhi Peter Yang, Stuart B. Goodman, Michiaki Takagi
    • Organizer
      Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology, Modern Rheumatology
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 節リウマチの滑膜におけるマクロファージサブタイプの変化に関する解析2024

    • Author(s)
      黄漢卿、高窪祐弥、宇野智洋、赤羽武、五十嵐貴裕、和根崎禎大、鈴木朱美、伊藤重治、高木理彰
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Periprosthetic joint pathology.2023

    • Author(s)
      Takagi M
    • Organizer
      The 67th Spring Congress of the Korean Orthopaedic Association Korea
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Current knowledge of rheumatoid arthritis.- Is rheumatoid hip is forgotten? -2023

    • Author(s)
      Takagi M
    • Organizer
      The 67th Spring Congress of the Korean Orthopaedic Association Korea
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis on autophagy-related molecules in macrophage subtype in the synovium of rheumatoid arthritis and Osteoarthritis2023

    • Author(s)
      Huang H, Takakubo Y, Maruyama M, Uno T, Akabane T, Igarashi T, Liu X, Takeda Y, Goodman SB, Takagi M
    • Organizer
      ORS 2023 Annual Meeting
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] 関節リウマチの滑膜におけるマクロファージのサブタイプ別のオートファジー関連タンパク質の解析.2022

    • Author(s)
      黄漢卿, 丸山真博, 髙窪祐弥, 劉興, 宇野智洋, 赤羽武, 五十嵐貴宏, 豊野修二, 和根崎禎大, 中島拓, 髙木 理彰
    • Organizer
      第37回日本整形外科学会基礎学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Pathologic overview of periprosthetic joint infections. To be or not to be?.2022

    • Author(s)
      Takagi M
    • Organizer
      2022 International Congress of the Korean Hip Society.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Macrophages Biology and Tissue Inflammation in Health and Disease2024

    • Author(s)
      Goodman S, Takagi M, Gallo J
    • Total Pages
      200
    • Publisher
      Elsevier Academic Press
    • Related Report
      2024 Annual Research Report
  • [Book] Macrophages Biology and Tissue Inflammation in Health and Disease2024

    • Author(s)
      Takagi M
    • Total Pages
      200
    • Publisher
      Elsevier Academic Press
    • Related Report
      2024 Annual Research Report
  • [Book] Macrophages Biology and Tissue Inflammation in Health and Disease2024

    • Author(s)
      Gallo J, Goodman SB, Takagi M
    • Total Pages
      200
    • Publisher
      Elsevier Academic Press
    • Related Report
      2024 Annual Research Report
  • [Book] Macrophages Biology and Tissue Inflammation in Health and Disease2024

    • Author(s)
      Goodman SB, Takagi M, Gallo J
    • Total Pages
      200
    • Publisher
      Elsevier Academic Press
    • Related Report
      2024 Annual Research Report
  • [Book] 股関節学の集大成 改訂2版2024

    • Author(s)
      高窪祐弥, 高木理彰
    • Total Pages
      1270
    • Publisher
      金芳堂
    • Related Report
      2024 Annual Research Report

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Published: 2022-04-19   Modified: 2026-01-16  

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