Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

非アルコール性脂肪性肝疾患を再現した腸・肝連結臓器チップの開発. 京都大学プレスリリース. 2023-04-07.Two-organ chip to answer fatty liver questions. 京都大学プレスリリース. 2023-04-07.Non-alcoholic fatty liver disease (NAFLD) afflicts a significant percentage of the population; however, no effective treatments have yet been established because of the unsuitability of in vitro assays and animal experimental models. Here, we present an integrated-gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) by co-culturing human gut and liver cell lines interconnected via microfluidics in a closed circulation loop, for the initiation and progression of NAFLD by treatment with free fatty acids (FFAs) for 1 and 7 days, respectively. Co-cultured Caco-2 gut-mimicking cells and HepG2 hepatocyte-like cells demonstrate the protective effects from apoptosis against FFAs treatment, whereas mono-cultured cells exhibit induced apoptosis. Phenotype and gene expression analyses reveal that the FFAs-treated gut and liver cells accumulated intracellular lipid droplets and show an increase in gene expression associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating the mechanisms of NAFLD

ピリジルシリルキ セイギョ ハンノウ ノ カイハツ ト シュウセキガタ ユウキ ゴウセイ エノ オウヨウ

京都大学0048新制・課程博士博士(工学)甲第11596号工博第2542号新制||工||1346(附属図書館)23239UT51-2005-D345京都大学大学院工学研究科合成･生物化学専攻(主査)教授 吉田 潤一, 教授 村上 正浩, 教授 杉野 目道紀学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDA

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To study drug response on human heart cells and predict drug induced cardiotoxicity, a microfluidic cell culture device with an integrated microelectrode array (MEA) is a promising approach. Here we integrate flexible MEA into microengineered and microfluidic in vitro human models, known as “Body-on-a-Chip”, during its fabrication. In this work, Au electrodes are covered by two layers of parylene C films, and then embedded in a polydimethylsiloxane (PDMS) layer, resulting in an easy-to-integrate process and compatible with soft-lithography. For a proof of fabrication concept, the impedance of individual electrode-electrolyte interfaces are measured to show a potential for network electrophysiology

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