Elucidation of interaction among shear stress, endothelial cells, and neural stem cells in vascular niche using perfusable microfluidic device
| Project/Area Number |
18K18360
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Nagata Shogo 東京大学, 生産技術研究所, 特任研究員 (40751441)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 神経幹細胞 / 血管性ニッチ / シェアストレス / マイクロ流体デバイス / 臓器チップ / 血管内皮細胞 / Organ-on-a-chip / マイクロデバイス |
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| Outline of Final Research Achievements |
In brain, vascular structure consisting of endothelial cells (ECs) and extracellular matrix functions as neural stem cell (NSC) niche. The ECs that are stimulated by the blood flow regulate the NSC characteristic including the stemness and differentiation potential. In this study, we constructed an NSC niche model consisting of NSCs derived from human pluripotent stem cells, human ECs, and extracellular matrix on a culture insert, and developed a microfluidic device that can apply shear stress to the ECs. We showed that the shear stress could induce not only the effects of ECs on cell function, but also the enhancement of stemness of the NSCs and suppression of differentiation into glial linage. By using microfabrication technology, we were able to reconstruct a highly biomimetic NSC niche model, and clarify some of the interrelationships between ECs, blood flow, and NSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
神経幹細胞(NSCs)は、血管内皮細胞(ECs)から成るNSCニッチに存在し、中枢神経系（CNS）の維持や組織障害後の再生を担っている。本研究では、これまでほとんど調べられてこなかったECsを介した血流刺激によるNSC制御機構を評価可能な培養システムを構築することに成功し、血流を模した流れ刺激は、ECsの代謝機能活性化を伴い、NSCsの幹細胞マーカーの発現上昇、およびグリア細胞マーカーの抑制を誘導することを見出した。これは、CNS恒常性維持や発生機構の解明のみならず、神経再生や神経疾患の病態機構の解明に寄与することが期待されている。また、神経再生誘導を目的とした創薬分野への貢献も期待できる。
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Report
(3 results)
Research Products
(4 results)
