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Bone regeneration using human induced pluripotent stem cell-derived mesenchymal stem cells

Research Project

Project/Area Number 17K10967
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionShowa University

Principal Investigator

Lee Sang Yang  昭和大学, 医学部, 講師 (40533732)

Co-Investigator(Kenkyū-buntansha) 新倉 隆宏  神戸大学, 医学研究科, 准教授 (40448171)
福井 友章  神戸大学, 医学部附属病院, 特定助教 (50437688)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨再生 / iPS細胞 / 間葉系幹細胞 / 軟骨分化 / 軟骨内骨化 / 細胞移植 / 再生医学
Outline of Final Research Achievements

We investigated whether implantation of chondrogenically differentiated human iPSCs-derived mesenchymal stem cells (iMSCs) could lead to bone regeneration of bone defects in mice. A 2-mm defect was created at the radius of nude mice. Chodrogenically differentiated iMSC pellets were then implanted in the defect. At week 8, 18 out of 21 (86%) radius in the treated group achieved bone healing, whereas 2 out of 11 (18%) radius in the control group achieved bone healing. At week 8, hitology revealed complete bone union in te treated group. At week 4, hypertrophic chondrocytes transitioning to the newly formed bone indicated that endochondral ossification was involved.
Our results for the first time demonstrated that grafting bone defects with chondrogenically differentiated iMSCs led to successful bone regeneration through endochondoral bone ossification. Our therapy could be a novel system to repair large bone defects.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、軟骨分化させたiMSCの細胞移植が、難治性骨折・骨欠損において、優れた再生能を有することが明らかとなった。本研究結果は、ヒトiPS細胞を用いた骨再生医療の将来の臨床応用の際の重要な情報となりうる。ヒトiPS細胞を用いた骨再生療法に関する知見が大きく広がり、ひいてはiPS細胞を用いた安全で確実な骨再生療法の実現への一歩となることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2019 2018

All Presentation (8 results) (of which Int'l Joint Research: 6 results)

  • [Presentation] Endochondral bone regeneration using chondrogenically differentiated human induced pluripotent stem cells.2019

    • Author(s)
      Lee SY, Arakura M, Fukui T, Kuroda R, Niikura T.
    • Organizer
      20th European Federation of National Associations of Orthopaedics and Traumatology Annual Congress.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endochondral Bone regeneration Using Chondrogenically Differentiated Human Induced Pluripotent Stem Cells.2019

    • Author(s)
      Lee SY, Arakura M, Kuroda R, Niikura T.
    • Organizer
      4th AO Trauma Asia Pacific Scientific Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone regeneration through endochondral ossification achieved with chondrogenically differentiated human induced pluripotent stem cells.2019

    • Author(s)
      Arakura M, Lee SY, Fukui T, Oe K, Takahara S, Kuroiwa Y, Kumabe Y, Kuroda R, Niikura T.
    • Organizer
      65th Annual Meeting of the Orthopaedic Research Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞による軟骨内骨化を介した骨再生の試み2019

    • Author(s)
      李相亮,新倉路生,福井友章,黒田良祐,新倉隆宏
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Endochondral bone tissue engineering using chondrogenically differentiated human induced pluripotent stem cells.2018

    • Author(s)
      Arakura M, Lee SY, Fukui T, Oe K, Takahara S, Kuroiwa Y, Kumabe Y, Oda T, Kuroda R, Niikura T.
    • Organizer
      The 5th Tissue Engineering and Regenerative Medicine International Society (TERMIS) World Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Endochondral bone regeneration using chondrogenically differentiated human induced pluripotent stem cells.2018

    • Author(s)
      Arakura M, Lee SY, Fukui T, Oe K, Takahara S, Kuroiwa Y, Kumabe Y, Oda T, Kuroda R, Niikura T.
    • Organizer
      The 16th Biennial Conference of the International Fracture Repair Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞による軟骨内骨化を介した骨再生療法2018

    • Author(s)
      2.新倉路生,李相亮,福井友章,大江啓介,高原俊介,黒岩祐,隈部洋平,黒田良祐,新倉隆宏
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Endochondral Bone Regeneration Using Chondrogenically Differentiated Human Induced Pluripotent Stem Cells2018

    • Author(s)
      Michio Arakura, Sang Yang Lee, Tomoaki Fukui, Shunsuke Takahara, Yu Kuroiwa, Yohei Kumabe, Ryosuke Kuroda, Takahiro Niikura
    • Organizer
      Annual meeting of Orthopaedic Research Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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