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2021 Fiscal Year Final Research Report

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

Research Project

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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
Keywords骨・軟骨代謝 / 再生医療 / iPS細胞 / 幹細胞
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.

Free Research Field

整形外科関連

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。

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Published: 2023-01-30  

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