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Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats

Research Project

Project/Area Number 20K18057
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Yoshitani Junya  金沢大学, 医学系, 協力研究員 (30800601)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords脂肪由来幹細胞 / インプラント周囲感染症 / 骨髄炎 / インプラント周囲感染 / 人工関節周囲感染 / インプラント感染症 / 抗生剤含有
Outline of Research at the Start

本研究の令和2年~3年度での具体的な目標は主に以下の3つである。
① 抗生剤とADSCsのcombined therapyがインプラント周囲感染モデルラットに対して従来
の治療法を上回る治療効果があるかどうかを検討すること
② ADSCsのインプラント周囲感染に対する治療効果を解析しそのメカニズムを解明すること
③ 臨床応用へ向けてより最適な投与方法 (全身投与、局所投与)、経路を探求すること

Outline of Final Research Achievements

This study aimed to evaluate the antimicrobial activity and therapeutic effect of local treatment with antibiotic-loaded adipose-derived stem cells (ADSCs) plus an antibiotic in a rat implant-associated infection model. Liquid chromatography/tandem mass spectrometry revealed that ADSCs cultured in the presence of ciprofloxacin for 24 h showed time-dependent antibiotic loading. The therapeutic effects of ADSCs plus antibiotics, antibiotics, and ADSCs were compared with no treatment as a control. Rats treated with ADSCs plus ciprofloxacin had the lowest modified osteomyelitis scores, abscess formation, and bacterial burden on the implant among all groups (P < 0.05). Thus, local treatment with ADSCs plus an antibiotic has an antimicrobial effect in implant-related infection and decrease abscess formation. Thus, our findings indicate that local administration of ADSCs with antibiotics represents a novel treatment strategy for implant-associated osteomyelitis.

Academic Significance and Societal Importance of the Research Achievements

脂肪由来幹細胞を用いた新たな感染治療の開発を行った。これまで難治性であったインプラント周囲感染症において、抗生剤と脂肪由来幹細胞を併用することで従来の治療を上回る効果が得られた。この結果はScientific Reports誌に投稿しまた海外でも発表を行っており一定の評価を得ている。今後は臨床試験へ向けて、大動物での実験系統を開発し、脂肪由来幹細胞と抗生剤の合剤として製薬開発を考慮する。本研究は新たなインプラント周囲感染症治療の基礎となるものである。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2021 2020

All Journal Article (1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats2020

    • Author(s)
      Yoshitani Junya、Kabata Tamon、Arakawa Hiroshi、Kato Yukio、Nojima Takayuki、Hayashi Katsuhiro、Tokoro Masaharu、Sugimoto Naotoshi、Kajino Yoshitomo、Inoue Daisuke、Ueoka Ken、Yamamuro Yuki、Tsuchiya Hiroyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 11182-11182

    • DOI

      10.1038/s41598-020-68184-y

    • Related Report
      2020 Research-status Report
  • [Presentation] Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats.2021

    • Author(s)
      吉谷純哉
    • Organizer
      The American Academy of Orthopaedic Surgeons
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗生剤処理した脂肪由来幹細胞を使用するインプラント周囲感染の新しい治療法の開発2021

    • Author(s)
      吉谷純哉
    • Organizer
      日本整形外科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 抗生剤処理した脂肪由来幹細胞を 使用するインプラント周囲感染の 新しい治療法の開発2021

    • Author(s)
      吉谷純哉
    • Organizer
      日本整形外科学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats2021

    • Author(s)
      Yoshitani Junya
    • Organizer
      American Academy of Orthopaedic Surgeons - AAOS
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2023-01-30  

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