Bio-fabrication of cerebral amyloid angiopathy model using Bio-3D printer and analysis of the pathophysiological mechanisms.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07890
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Saga University
• Principal Investigator: Hara Hideo 佐賀大学, 医学部, 客員研究員 (00260381)
• Co-Investigator(Kenkyū-buntansha): 中山 功一 佐賀大学, 医学部, 教授 (50420609)
• Project Period (FY): 2020-04-01 – 2023-03-31
• 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

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.

Free Research Field

神経内科学

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。