| Project/Area Number |
17K09758
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Saga University |
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Principal Investigator |
Hara Hideo 佐賀大学, 医学部, 教授 (00260381)
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| Co-Investigator(Kenkyū-buntansha) |
中山 功一 佐賀大学, 医学部, 教授 (50420609)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脳アミロイド血管症 / バイオ3D プリンター / スフェロイド / Aβ40/42 / アミロイド前駆蛋白遺伝子 / 脳神経疾患 / アルツハイマー型認知症 / アミロイド血管症 |
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| Outline of Final Research Achievements |
Cerebral amyloid angiopathy (CAA) is a small vessel disease by the deposition of amyloid protein (mainly Ab40) in cortical vessels and results in vessel fragility and intracerebral hemorrhages. We established a scaffold-free system for assembling cell constructs using an automated Bio-3D printer. We aim to create an in vitro model of CAA using a bio-3D printer, and analyze the pathophysiology and mechanisms that causes CAA. Immunostaining against a-smooth muscle actin (a-SMA) showed the smooth muscle phenotype of cells in the inner layers in control, however, decreased SMA stainability in the presence of Ab40. The tensile strength of the tubular vessels were tested with a cyclic tension test, applied with a tensometer, revealed decreased elasticity and strength in the presence of Ab40. CAA in vitro model showed the different stainability of collagen, SMA and CD31, and decreased elasticity and strength of tubular vessels compared to control, suggesting vessel fragility.
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| Academic Significance and Societal Importance of the Research Achievements |
脳アミロイド血管症は血管壁に主としてAβ40が蓄積するため血管壁が脆弱となり、しばしば皮質の大出血を起こす。最近では脳アミロイド血管症関連の脳炎症状態も報告されているが、その機序は解明されていない。我々はバイオ3D プリンターを用いた脳アミロイド血管症のモデル血管を作成し、脳アミロイド血管症が起こるメカニズムを解析し、さらに血管壁の破綻による大出血や血管周囲炎症を予防する治療法の開発を目的とした。この研究により血管壁へのAβ沈着を除去できる治療法の開発や血管壁にAβ沈着するメカニズムも解明し、予防的な治療法の開発にもつながると考えられる。
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