| Project/Area Number |
17K15945
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Tottori University |
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Principal Investigator |
ITABA Noriko 鳥取大学, 医学(系)研究科(研究院), 助教 (70457167)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 間葉系幹細胞 / 肝線維化 / セクレトーム / エクソソーム / 肝硬変 |
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| Outline of Final Research Achievements |
This research is aimed to develop a novel therapy for liver cirrhosis by identifying hepatic fibrosis-reducing factors of therapeutic cell sheets for liver disease derived from mesenchymal stem cells (MSCs) engineered with original compound, IC-2, and by constructing exosomes targeted to activated hepatic stellate cells.
In this study, it was clarified that IC-2-treated MSCs-derived secretome suppressed activation of hepatic stellate cells potently compared to those exosomes. The secretome included thioredoxin, Dkk-1, which were effective to inhibit hepatic stellate cells activation, and various MMPs which acted fibrinolysis. These data demonstrate that utilizing IC-2-treated MSCs-derived secretome may serve as the development of a simple and novel therapy for liver cirrhosis in cell-free system.
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| Academic Significance and Societal Importance of the Research Achievements |
肝硬変は国内の年間死亡者数が約17,000例に達しながら、いまだ有効な治療薬が存在しない。研究者らが開発した、温度応答性培養皿上で間葉系幹細胞(MSCs)に低分子化合物IC-2を添加し作製する「肝疾患治療用細胞シート」は、肝硬変の新規治療法となると期待されるが、外科手術を伴うため侵襲性が高く、すべての患者への適応は困難であると想定される。本研究ではIC-2をMSCsに添加することで、肝線維化抑制に有効な因子を増強したセクレトームが得られることを示した。本研究の成果は、簡便かつセルフリー、外科手術も不要な肝硬変患者の新規治療法として将来的に応用可能であり、学術的、社会的に意義深い研究である。
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