We describe an expanded modular gastrointestinal (GI) tract–liver system by co-culture of primary human intestinal epithelial cells (hIECs) and 3D liver mimic. The two organ body-on-chip design consisted of GI and liver tissue compartments that were connected by fluidic medium flow driven via gravity. The hIECs and HepG2 C3A liver cells in the co-culture system maintained high viability for at least 14 days in which hIECs differentiated into major cell types found in native human intestinal epithelium and the HepG2 C3A cells cultured on 3D polymer scaffold formed a liver micro-lobe like structure. Moreover, the hIECs formed a monolayer on polycarbonate membranes with a tight junction and authentic TEER values of approximately 250 Ω cm² for the native gut. The hIEC permeability was compared to a conventional permeability model using Caco-2 cell response for drug absorption by measuring the uptake of propranolol, mannitol and caffeine. Metabolic rates (urea or albumin production) of the cells in the co-culture GI–liver system were comparable to those of HepG2 C3A cells in a single-organ fluidic culture system, while induced CYP activities were significantly increased in the co-culture GI tract–liver system compared to the single-organ fluidic culture system. These results demonstrated potential of the low-cost microphysiological GI–liver model for preclinical studies to predict human response.

中文翻译：

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使用人肠道细胞的原代培养和肝细胞的3D培养的无泵芯片上人体模型。

我们通过人类原代肠上皮细胞（hIECs）和3D肝模拟物的共培养来描述扩展的模块化胃肠道（GI）肝-肝系统。两种器官片上设计均由胃肠道和肝脏组织隔室组成，它们通过重力驱动的流体介质流相连。共培养系统中的hIECs和HepG2 C3A肝细胞保持了至少14天的高存活力，其中hIECs分化为在天然人肠上皮细胞中发现的主要细胞类型，并且在3D聚合物支架上培养的HepG2 C3A细胞形成了肝微管。瓣状结构。此外，hIEC在聚碳酸酯膜上形成一个单层，具有紧密的连接，真实的TEER值约为250Ωcm ²对于本地的肠子。通过测量普萘洛尔，甘露醇和咖啡因的摄取，将hIEC渗透性与使用Caco-2细胞反应进行药物吸收的常规渗透性模型进行了比较。共培养GI-肝系统中细胞的代谢速率（尿素或白蛋白产生）与单器官流体培养系统中的HepG2 C3A细胞相当，而共培养GI中诱导的CYP活性显着增加与单器官流体培养系统相比，导管-肝脏系统。这些结果证明了低成本微生理GI-肝模型在临床前研究中预测人类反应的潜力。