A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells.
A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells.
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DOI：
10.1039/c8lc00111a
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发表时间：
2018-07-10
期刊：
影响因子：
6.1
通讯作者：
Shuler ML
中科院分区：
文献类型：
--
作者：
Chen HJ;Miller P;Shuler ML
我们描述了一个扩展的模块化胃肠道(GI) -肝脏系统通过共同培养原代人肠上皮细胞（hIECs）和三维肝脏模拟物。两个器官片体设计由胃肠道和肝脏组织室组成，它们通过重力驱动的流体介质流连接。hIECs和HepG2 C3A肝细胞在共培养体系中保持了至少14天的高活力，hIECs分化为天然人肠上皮的主要细胞类型，HepG2 C3A细胞在3D聚合物支架上培养形成肝脏微叶样结构。此外，hiec在聚碳酸酯膜上形成一层紧密连接的单层，天然肠道的真实TEER值约为250 Ωcm2。通过测量心得安、甘露醇和咖啡因的摄取，利用cco -2细胞对药物吸收的反应，将hIEC通透性与传统通透性模型进行比较。胃肠道-肝脏共培养系统中细胞的代谢率（尿素或白蛋白产量）与单器官流体培养系统中的HepG2 C3A细胞相当，而胃肠道-肝脏共培养系统中诱导的CYP活性与单器官流体培养系统相比显著增加。这些结果证明了低成本的微生理gi -肝脏模型在临床前研究中预测人体反应的潜力。
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 Ωcm2 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.
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DOI：
10.1038/nrgastro.2016.125
发表时间：
2016-09-01
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Dickson, Iain
通讯作者：
Dickson, Iain
影响因子：
2.8
作者：
Chi, Meiying;Yi, Banya;Park, Sungsu
通讯作者：
Park, Sungsu
DOI：
10.1152/ajpcell.1998.275.4.c988
发表时间：
1998-10-01
影响因子：
5.5
作者：
Kim, EC;Zhu, YT;Lance, P
通讯作者：
Lance, P
影响因子：
46.9
作者：
Chen HJ;Wei Z;Sun J;Bhattacharya A;Savage DJ;Serda R;Mackeyev Y;Curley SA;Bu P;Wang L;Chen S;Cohen-Gould L;Huang E;Shen X;Lipkin SM;Copeland NG;Jenkins NA;Shuler ML
通讯作者：
Shuler ML
影响因子：
4.6
作者：
Oleaga C;Bernabini C;Smith AS;Srinivasan B;Jackson M;McLamb W;Platt V;Bridges R;Cai Y;Santhanam N;Berry B;Najjar S;Akanda N;Guo X;Martin C;Ekman G;Esch MB;Langer J;Ouedraogo G;Cotovio J;Breton L;Shuler ML;Hickman JJ
通讯作者：
Hickman JJ