| Project/Area Number |
16K16395
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Tokyo Medical and Dental University (2018)
National Institute of Advanced Industrial Science and Technology (2016-2017) |
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Principal Investigator |
KUSHIGE Hiroko 東京医科歯科大学, 難治疾患研究所, プロジェクト助教 (90723065)
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| Research Collaborator |
TAKAYAMA Yuzo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Organ-on-a-chip / 自律神経 / 褐色脂肪 / 褐色脂肪細胞 / 生体医工学 / 微細加工 / 細胞・組織 / 分化誘導 |
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| Outline of Final Research Achievements |
Microfluidic organ-on-a-chip (OOC) is an attractive in vitro platform designed to model the functional units of organs. Recently, we established a protocol for differentiation of autonomic neurons (ANs) from human iPS cells. Based on the technique, we aimed to construct OOCs for studying interactions between brown adipocytes and ANs generated from patients. In order to obtain valuable information for analyses on the chip, we performed genomics and metabolomics profiling in growing mouse brown adipose tissues. Furthermore, we established an iPS cell line derived from a patient with Familial dysautonomia (FD) and genome editing iPS cell lines which are repaired a point mutation of FD. By using these cell lines, we performed gene expression profiling during AN differentiation and investigated neuronal regulations of cardiac behaviors. In this study, we provided the basis of OOCs for understanding the pathogenic mechanisms of metabolic diseases and evaluating the efficacy of new drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
従来のモデル動物を用いた生体内実験においては、複数組織にわたる神経シグナルやホルモン因子をリアルタイムに追跡することは困難であった。これに対して、生体外で患者個々人の組織間ネットワークを再構成することができれば、電気計測システムやバイオイメージング手法、代謝アッセイなどの解析を適宜融合することで、その中心的な役割を果たす自律神経シグナルやホルモン因子などの動的なシグナルを複数組織においてリアルタイムかつ同時に計測することが可能となる。本研究では患者個々人の細胞を用いて自律神経を分化誘導し、複数の組織間ネットワークを解析するためのデバイス開発に向けた礎を築いた。
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