| Project/Area Number |
18K18359
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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 90110:Biomedical engineering-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵島 / 炎症 / マクロファージ / 凝集体 / 糖尿病 / インスリン / 酸素 / マイクロウェル / ヒトiPS細胞 |
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| Outline of Final Research Achievements |
In this study, a culture system was developed that reproduces in vitro cell death of pancreatic β-cells and infiltration of immune cells into the islets, which caused by the inflammation. After formation of pancreatic islet-like aggregates using several kinds of endocrine pancreas cells on a plate with microwells on the bottom surface. The inflammation was induced by IL-1β and IFN-γ stimulation, and co-culture with macrophages was performed. IL-1β stimulation of pancreatic β cells increased the productivity of inflammatory factors such as CCL2 and CCL3, and co-culture with macrophages markedly caused apoptosis and cell death. It was suggested that pancreatic β-cell damage could be reproduced by IL-1β stimulation from macrophages in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病研究や新規糖尿病治療薬の開発において，専ら動物実験や動物由来の初代膵島を用いた検討が行われているが，ヒトでの生理的な応答を十分に再現することは難しい. そして，初代培養では単離後に機能が著しく低下するため，評価系として均質性を維持することは困難である．本研究の成果は，生体内の炎症による膵β細胞の細胞死と機能障害を再現する膵島組織培養の可能性を示すものであり，ヒトiPS細胞由来膵島構成細胞や細胞株など様々な細胞種に応用が可能であることから，糖尿病研究や創薬分野の加速化につながることが期待される.
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