Due to a more physiological reproduction of the in vivo situation, liver-on-a-chip devices in recent studies have shown higher sensitivity and accuracy for hepatotoxicity testing compared to traditional in vitro liver models. In this context, this work presents an original microfluidic device mimicking 3D hepatic cords organized radially, like in the liver lobule. Ten cell-culture chambers seeded at a high density are disposed with a parallelized flow that emulates blood flow from the portal triad to the central vein in the liver lobule. Using this device, on-chip differentiation of human HepaRG-Hepatoblast (HepaRG-HB) to HepaRG-Hepatocytes (HepaRG-HC) has been studied in terms of self-organization capabilities, bile canaliculi formation and albumin expression. Our results indicate that due to the design of the cell culture chamber, which mechanically constrains tissue proliferation, and the physiologically relevant microfluidic flow condition used during tissue development, the HepaRG-HBs in the device can proliferate, self-organize, and spontaneously differentiate in a DMSO free medium forming long, directional bile canaliculi. On the contrary, under the same conditions, differentiated HepaRG-HC is observed to aggregate without long bile canaliculi and form tissues resembling traditional HepaRG-HC cultures. © 2024 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.

中文翻译：

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利用径向流对肝索进行片上分化

由于体内情况更加生理再现，与传统的体外肝脏模型相比，最近研究中的肝脏芯片设备在肝毒性测试方面表现出更高的灵敏度和准确性。在这种背景下，这项工作提出了一种原始的微流体装置，模仿放射状组织的 3D 肝索，就像在肝小叶中一样。以高密度接种的十个细胞培养室布置有平行流，模拟从门静脉三联体到肝小叶中央静脉的血流。使用该设备，在自组织能力、胆小管形成和白蛋白表达方面研究了人 HepaRG-肝母细胞 (HepaRG-HB) 与 HepaRG-肝细胞 (HepaRG-HC) 的芯片分化。我们的结果表明，由于细胞培养室的设计机械地限制了组织增殖，以及组织发育过程中使用的生理相关的微流体条件，装置中的 HepaRG-HBs 可以在细胞中增殖、自组织和自发分化。不含 DMSO 的培养基，形成长的、定向的胆小管。相反，在相同条件下，观察到分化的HepaRG-HC在没有长胆小管的情况下聚集并形成类似于传统HepaRG-HC培养物的组织。 © 2024 日本电气工程师协会。由 Wiley 期刊有限责任公司出版。