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Elucidation of the function of cartilage membrane using iPSC-derived cartilage

Research Project

Project/Area Number 18H02924
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOsaka University (2020-2021)
Kyoto University (2018-2019)

Principal Investigator

Akihiro Yamashita  大阪大学, 医学系研究科, 助教 (00636855)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords骨・軟骨代謝 / 再生医療 / iPS細胞 / 幹細胞 / 骨・軟骨代謝学 / 骨軟骨代謝学 / 再生 / 軟骨 / 骨代謝学 / 再生医学 / 軟骨再生 / 軟骨膜 / 軟骨周膜
Outline of Final Research Achievements

New cell and tissue sources are needed for the regenerative treatment of articular cartilage damage. Hyaline cartilage tissue particles derived from human iPSCs (hiPS-Carts) are one candidate source. hiPS-Cart consists of cartilage at the center and perichondrium-like membrane that wraps around the cartilage.When transplanted to fill the defects of articular cartilage, hiPS-Carts form repair tissue by integrating with each other. RNA sequencing analysis identified a higher expression of FGF18 in the perichondrium-like membrane in hiPS-Carts compared with the central cartilage. The addition of FGF18 accelerated the integration of hiPS-Carts, whereas addition of FGFR inhibitor inhibited it. These results suggest that FGF18 secreted from the perichondrium-like membrane plays a role in the integration of hiPS-Carts. Understanding the integration mechanism of hiPS-Carts is expected to contribute to the realization of regenerative treatment for patients with articular cartilage damage.

Academic Significance and Societal Importance of the Research Achievements

われわれはヒトiPS細胞から分化誘導して作製した軟骨を損傷部に移植する新規治療法の開発を目指している。本研究の結果、軟骨膜に発現するFGF18が軟骨組織の融合に重要な役割を果たしていることが明らかとなった。iPS細胞由来軟骨による組織再生には軟骨膜を温存することが重要である。この知見をもとに大型動物への有効性試験を経て臨床応用が可能となると考えられる。またより効率の良い軟骨分化誘導法を確立できる可能性がある。よって本研究の成果は、iPS細胞由来軟骨を用いた再生治療の治癒メカニズムの一端を解明するものであり、関節軟骨損傷に対する新規治療法の開発に貢献すると考える。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (9 results)

All 2022 2021 2020 2018

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Generation of Monkey Induced Pluripotent Stem Cell-Derived Cartilage Lacking Major Histocompatibility Complex Class I Molecules on the Cell Surface2022

    • Author(s)
      Okutani Yuki、Abe Kengo、Yamashita Akihiro、Morioka Miho、Matsuda Shuichi、Tsumaki Noriyuki
    • Journal Title

      Tissue Engineering Part A

      Volume: 28 Issue: 1-2 Pages: 94-106

    • DOI

      10.1089/ten.tea.2021.0053

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent progress of animal transplantation studies for treating articular cartilage damage using pluripotent stem cells2021

    • Author(s)
      Yamashita Akihiro、Tsumaki Noriyuki
    • Journal Title

      Development, Growth & Differentiation

      Volume: 63 Issue: 1 Pages: 72-81

    • DOI

      10.1111/dgd.12706

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects2021

    • Author(s)
      Tam Wai Long、Freitas Mendes Luis、Chen Xike、Lesage Raphaelle、Van Hoven Inge、Leysen Elke、Kerckhofs Greet、Bosmans Kathleen、Chai Yoke Chin、Yamashita Akihiro、Tsumaki Noriyuki、Geris Liesbet、Roberts Scott J.、Luyten Frank P.
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 12 Issue: 1 Pages: 513-528

    • DOI

      10.1186/s13287-021-02580-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Culture substrate‐associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells2020

    • Author(s)
      Yamashita Akihiro、Yoshitomi Hiroyuki、Kihara Shunsuke、Toguchida Junya、Tsumaki Noriyuki
    • Journal Title

      STEM CELLS Translational Medicine

      Volume: 10 Issue: 1 Pages: 115-127

    • DOI

      10.1002/sctm.20-0058

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage2020

    • Author(s)
      Takei Yoshiaki、Morioka Miho、Yamashita Akihiro、Kobayashi Tomohito、Shima Nobuyuki、Tsumaki Noriyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 12794-12805

    • DOI

      10.1038/s41598-020-69641-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integration Capacity of Human Induced Pluripotent Stem Cell-Derived Cartilage.2018

    • Author(s)
      Chen X, Yamashita A, Morioka M, Senba T, Kamatani T, Watanabe A, Kosai A, Tsumaki N.
    • Journal Title

      Tissue Eng Part A,

      Volume: 25 Issue: 5-6 Pages: 437-445

    • DOI

      10.1089/ten.tea.2018.0133

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Considerations in hiPSC-derived cartilage for articular cartilage repair.2018

    • Author(s)
      Yamashita A, Tamamura Y, Morioka M, Karagiannis P, Shima N, Tsumaki N
    • Journal Title

      Inflamm Regen.

      Volume: 38 Issue: 1 Pages: 1-7

    • DOI

      10.1186/s41232-018-0075-8

    • NAID

      120006937645

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来軟骨を用いた限局した関節軟骨治療法の開発2020

    • Author(s)
      山下 晃弘, 妻木 範行
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Application of iPS cell technologies to treat skeletal disease2020

    • Author(s)
      Yamashita A, Tsumaki N
    • Organizer
      第68回国際歯科研究学会日本部会 (JADR) 総会・学術大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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