2021 Fiscal Year Final Research Report
Investigation of the mechanism and prevention for ischemia-reperfusion injury by using blood-brain barrier-on-a-chip
| Project/Area Number |
19H04435
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
立川 正憲 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (00401810)
吉野 大輔 東京農工大学, 工学(系)研究科(研究院), 准教授 (80624816)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | マイクロ・ナノデバイス / 細胞・組織 / 生物・生体工学 / 流体工学 / ナノバイオ / 血液脳関門 / 微小血管網 / 虚血再灌流障害 |
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| Outline of Final Research Achievements |
Microvascular network was created by culturing vascular endothelial cells and fibroblasts mixed in a fibrin gel placed in a chip with controllability of oxygen concentration and mechanical and chemical stimuli. Gas mixtures were supplied to the gas channels in the chip to generate a steady state of normoxic or hypoxic conditions at oxygen concentration of 21% or 0.3%, respectively, or repeatedly change the two oxygen conditions. Immediately after the reoxygenation from the hypoxic state, reactive oxygen species were produced, and the permeability of microvascular network was significantly increased. The same tendency of the permeability increase by changes of oxygen concentration was observed in the microvascular network that mimicked human blood-brain barrier with vascular endothelial cells, pericytes, and astrocytes.
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| Free Research Field |
生体工学
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| Academic Significance and Societal Importance of the Research Achievements |
虚血再灌流は、急性の低酸素負荷と再酸素化、血流による力学的な刺激を血管に作用させ、血管障害や臓器障害を誘発する可能性がある。脳の虚血再灌流障害は高齢者のみならず新生児にとっても深刻な問題であるが、その発生機序は完全には理解されておらず、早急な原因究明と予防法の確立が求められている。本研究は、生体外に形成した微小血管網に対し、酸素濃度制御下の動態および機能の評価を可能にし、再酸素化による微小血管網の物質透過性の増加と活性酸素の関与を示した。活性酸素の発生に対して血管内皮細胞の結合性を維持する対策が重要であることが示唆され、この知見は虚血再灌流障害を防止する技術の確立に寄与する。
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