Spheroid-based blood-brain barrier (BBB) model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: The University of Tokyo
• Principal Investigator: Shima Ai 東京大学, 大学院情報理工学系研究科, 特任助教 (50757309)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 組織工学 / organ-on-a-chip / マイクロ流路

Outline of Final Research Achievements

The purpose of this study was to arrange blood-brain barrier (BBB) spheroids, which consist of cells that constitute BBB, in a microarray and demonstrate a high-throughput drug permeability test using them. I prepared spheroids using commercially available human primary brain endothelial cells and succeeded in capturing them on a microarray. A fluorescently labeled dextran solution was administered to the spheroids in the microarray, cross-sectional images of the identified spheroid were taken by confocal microscope over time, and the fluorescence intensity of the images were measured. An increase of fluorescence intensity was observed. In addition, the uptake test of the fluorescent substrate was possible on the microarray even in the presence of flow stimulation. However, the physiological characteristics of barrier function of BBB were not reproduced.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

BBBは高いバリア機能によって、血液中から脳内への有害物質の侵入を防いでいるが、医薬品の移行が阻害される場合も多い。そこで、中枢神経系を標的とした医薬品の開発においてはヒトBBBの透過性を調べることが重要である。動物モデルやカルチャーインサートなどの多孔質メンブレンを利用したBBBモデルが一般に用いられるが、透過性試験の効率は高くない。本研究では、より効率的な透過性試験の実施を目指して、BBBスフェロイドとマイクロアレイを組み合せることで、簡便に、多数のサンプルを一度に評価可能な系を提案し、実現可能性を検証した。