Bio-fabrication of cerebral amyloid angiopathy model using Bio-3D printer and analysis of the pathophysiological mechanisms.
| Project/Area Number |
20K07890
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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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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Saga University |
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Principal Investigator |
Hara Hideo 佐賀大学, 医学部, 客員研究員 (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) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / アミロイドベータ蛋白 / アルツハイマー病 / アルツハイマー型認知症 / バイオ3Dプリンター / アミロイドβ蛋白 / 3Dバイオプリンター / アミロイド血管症 / 血管 / 炎症 / 血液脳関門 |
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| Outline of Research at the Start |
脳アミロイド血管症は血管壁に主としてAβ40が蓄積し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。高齢化とともに脳アミロイド血管症を発症する症例が増えており治療法も開発されていない。またCAAを3次元的にin vitroで作成された報告は未だにない。
我々のこれまでの研究によりCAAのモデル血管をin vitroで作成したので、血管壁のAβ沈着を除去できる様々な治療法の開発を目的とする。血管壁にAβ沈着するメカニズムも解明できた場合には、予防的な治療法の開発も着手する。
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| Outline of Final Research Achievements |
We established a scaffold-free system for assembling cell constructs using an automated Bio-3D printer with the Kenzan method. We aim to create an in vitro model of CAA using this method, and analyze the pathophysiology and mechanisms that causes CAA. We assemble multicellular spheroids composed of normal human dermal fibroblasts, smooths muscle cell and human umbilical vein endothelial cell to construct tubular vessels and cultured in the presence of Abeta 40 peptides. Immunostaining against Abeta 40 showed the amyloid deposition on the outer layer of vessel wall at the site that matches collagen IV positive extracellular matrix, but not coincident with SMA. The tensile strength of the tubular vessels revealed decreased elasticity and strength in the presence of Abeta 40. 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の病態機序や治療法は未だ解明されていない。この研究により脳アミロイド血管症のモデル血管をin vitroで作成することにより、血管壁のAβ沈着を除去できる様々な治療法の開発に応用できると考えられる。また血管壁にAβ沈着するメカニズムも解明できた場合には、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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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation2023
Author(s)
Y Soo, A Zietz, B Yiu, V C.T. Mok, A A Polymeris, D Seiffge, G Ambler, D Wilson, T Wai Hong Leung, S.F Tsang, W.C.J.Abrigo, C Cheng, K-J Lee, et al.
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Journal Title
Annals of Neurology
Volume: in press
Issue: 1
Pages: 61-74
DOI
Related Report
Peer Reviewed
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[Journal Article] Meta-iodobenzylguanidine myocardial scintigraphy in Perry disease2021
Author(s)
Mishima T, Fujioka S, Nishioka K, Li Y, Sato K, Houzen H, Yabe I, Shiomi K, Eriguchi M, Hara H, Hattori N, Tsuboi Y.
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Journal Title
Parkinsonism and related disorders
Volume: In press
Pages: 49-53
DOI
Related Report
Peer Reviewed
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[Journal Article] Olfactory-cognitive index distinguishes involvement of frontal lobe shrinkage, as in sarcopenia from shrinkage of medial temporal areas, and global brain, as in Kihon Checklist frailty/dependence, in older adults with progression of normal cognition to Alzheimer's disease.2021
Author(s)
Iritani O, Okuno T, Miwa T, Makizako H, Okutani F, Kashibayashi T, Suzuki K, Hara H, Mori E, Omoto S, Suzuki H, Shibata M, Adachi H, Kondo K, Umeda-Kameyama Y, Kodera K, Morimoto S.
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Journal Title
Geriatr Gerontol Int
Volume: 21
Issue: 3
Pages: 291-298
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Subclinical acute Ischemic lesions and cerebrospinal fluid profiles in intracerebral hemorrhage: HAGAKURE STUDY.2020
Author(s)
Yoshikawa M, Yakushiji Y, Tanaka J, Ogata A, Nishihara M, Eriguchi M, Suzuyama K, Nagaishi Y, Mizoguchi M, Shichijo C, Ide T, Katsuki Y, Kawamoto K, Abe T, Hara H
Organizer
European stroke organisation - World stroke organization
Related Report
Int'l Joint Research
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[Presentation] Total Small Vessel Disease Score among Ischemic Stroke Subtypes: HAGAKURE study.2020
Author(s)
Iida K, Yakushiji Y, Tanaka J,Nishihara M, Eriguchi M, Suzuyama K, Shichijo C, Nagaishi Y, Megumi M, Suetsugu N, Ide T, Yoshikawa M, Hoshino Y, Katsuki Y, Hideo H
Organizer
European stroke organisation - World stroke organization (ESO-WSO)
Related Report
Int'l Joint Research
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