Liver fibrosis investigation using iPSCs hepatic derived organ on chip

使用 iPSC 肝源性芯片进行肝纤维化研究

• 批准号: 22H03934
• 负责人: LECLERC Eric
• 金额: $ 11.07万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22H03934/
• 关键词: liver disease model; stem cells; organ on chip; fibrosis; liver; liver on chip; pluripotent stem cells; disease model; multi cellular cultures; MicroPhysiologicalSystem; Liver; iPSCs

We are planning to use organ on chip and hepatocyte like cells (HLCs), liver sinusoidal like cells (LSECs) and stellate like cells (HSCs) triple coculture as a liver fibrosis model. The fibrosis will be triggered either by palmitic acid to access physio pathological progression from steatosis to liver fibrosis; either directly by the TGF beta that is a pro fibrotic factor inducing stellate cells activation.We published a paper dealing with HLCs and LSECs cocultures. The paper focuses on the characterisation of the coculture inside the biochips in the healthy condition. We established that the biochip is relevant model to express important liver function related to zonation. Then we extended our characterisation using the three cultures in healthy condition as well. The triple culture seems to show an important development of the HSC in biochip that we are now analysing. In parallel single cells sequencing analysis were performed on preliminary tri culture experiments to extract the cell subpopulation of HLCs, LSECs, HSCs in biochips. We also include control conditions and conditions exposed to TGF beta.

我们计划使用器官芯片和肝细胞样细胞（HLC）、肝窦状隙样细胞（LSEC）和星状细胞样细胞（HSC）三元共培养作为肝纤维化模型。纤维化将由棕榈酸触发，以获得从脂肪变性到肝纤维化的生理病理学进展;或者直接由TGF β触发，TGF β是诱导星状细胞活化的促纤维化因子。本文重点研究了健康条件下生物芯片内共培养物的特性。我们建立了生物芯片是表达与肝分区相关的重要肝功能的相关模型。然后，我们也使用健康状态下的三种培养物来扩展我们的表征。三重培养似乎显示了我们正在分析的生物芯片中HSC的重要发展。 在平行的单细胞测序分析上进行初步的三培养实验，以提取生物芯片中的HLC、LSEC、HSC的细胞亚群。我们还包括对照条件和暴露于TGF β的条件。

项目成果

Organ on chip in predictive biology and applied pharmacology

器官芯片在预测生物学和应用药理学中的应用

• 发表时间: 2023
• 作者: Danoy Mathieu;Poulain St?phane;Jellali Rachid;Scheidecker Benedikt;Tauran Yannick;Leduc Marjorie;Bruce Johanna;Kim Soo Hyeon;Kido Taketomo;Miyajima Atsushi;Sakai Yasuyuki;Leclerc Eric;Leclerc
• 通讯作者: Leclerc

UTC/ Compiegne(フランス)

UTC/贡比涅（法国）

LIMMS

实验室管理系统

Cellenion(フランス)

塞勒尼翁（法国）

Sakai Nishikawa lab

酒井西川实验室