| Project/Area Number |
18K16618
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Asai Shuji 名古屋大学, 医学部附属病院, 講師 (00770893)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 腱 / 変性 / ヒアルロン酸 / 間葉系幹細胞 / MAPK |
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| Outline of Final Research Achievements |
In this study, using a mouse Achilles tendon injury model and progenitor-like cells isolated from the injured tendon, we found the followings: (1) high molecular weight hyaluronic acid inhibits chondrogenic differentiation of injured tendon-derived progenitor-like cells and promotes tenogenic differentiation, (2) 4-Methylumbelliferone (4-MU), an inhibitor of hyaluronan synthesis, promotes chondrogenic differentiation of injured tendon-derived progenitor-like cells, 3) high molecular weight hyaluronic acid inhibits heterotopic mineralization in a mouse Achilles tendon injury model, and 4) 4-MU promotes heterotopic mineralization. These results suggest that high molecular weight hyaluronic acid may inhibit degeneration and promote repair of injured tendons. Further studies are needed to elucidate the molecular mechanism.
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| Academic Significance and Societal Importance of the Research Achievements |
腱損傷部の修復を促進するために，骨髄や脂肪由来の間葉系幹細胞に成長因子を投与することにより腱分化を誘導し，それらの細胞をscaffoldとともに損傷部位に移植する研究が行われている．しかし，いずれの研究も動物実験段階であり，完全な腱組織の獲得には至っていない．また，臨床応用するためには，ドナー細胞を採取する侵襲が患者に加わることが問題のひとつである．本研究で用いた方法により，腱損傷部に自然誘導される幹細胞の腱分化を促進できる可能性があり，ドナー細胞を採取する侵襲を避けることができる．また，ヒアルロン酸は既承認薬であり安全性が担保されており，本研究で得られた成果は臨床に応用しやすいと考える．
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