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歯肉幹細胞由来エクソソームは、M2分化を誘導し、歯槽骨吸収を抑制した

中尾, 雄紀 NAKAO, Yuki ナカオ, ユウキ 九州大学

2021.05.31

概要

間葉系幹細胞(MSC)は、その多分化能から再生医療における代表的なツールであると考えられてきたが、近年ではその分泌能が特に注目されており、その中心的役割を担う細胞外分泌物がエクソソームである。

今回、歯肉から単離した幹細胞(GMSC)の培養上清からエクソソームを精製し、歯周病治療への応用への可能性について検証を行った。GMSC 由来エクソソームは、炎症性のマクロファージを組織修復性の M2 マクロファージへと転換することで抗炎症能を発揮することを発見し、マウスの創傷治癒モデルにおいても治癒効果を確認した。さらに GMSC を炎症刺激(TNF-α)することで、ネガティブフィードバック機構により増強することを発見したが、その分子機構においてエクソソームの CD73 が重要であることを解明した。

マウス歯周炎モデルにおいても、GMSCs 由来エクソソーム注入により歯槽骨の吸収が有意に抑制され、TNF-α刺激 GMSC 由来エクソソームで著明な治療効果が確認された。さらに、GMSC 由来エクソソームによる骨吸収抑制効果の分子機構を解析した結果、GMSC への TNF-α刺激で誘導されるエクソソーム内包 miRNA(miR-1260b)をマイクロアレイ解析により同定し、その標的である Wnt5a-JNK 経路の抑制を介して破骨細胞活性化因子 RANKL の発現抑制することで、歯周炎モデルの骨吸収を抑制することを解明した。

以上から、TNF-α刺激により抗炎症効果が増強した GMSCs 由来エクソソームは、組織修復性 M2 マクロファージ誘導と歯槽骨吸収抑制効果を介して、新たな歯周病治療の標的となり得る可能性を明らかにした。

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参考文献

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