Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines
Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines
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DOI：
10.1016/j.tiv.2014.02.005
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发表时间：
2014-08-01
影响因子：
3.2
通讯作者：
Leclerc, Eric
中科院分区：
文献类型：
--
作者：
Bricks, Thibault;Paullier, Patrick;Leclerc, Eric
我们开发了一种新的生物模型来模拟肠道和肝脏之间的器官相互作用。我们将聚碳酸酯细胞培养插入物和微流体生物芯片耦合在一个集成流体平台中，允许动态共培养（称为 IIDMP，即动态微流体平台中的集成插入物）。使用 Caco-2 TC7 细胞模拟肠室，使用 HepG2 C3A 模拟肝脏。我们表明，与传统的插入培养物培养物相比，在生物反应器中共培养期间，Caco-2 TC7 的活力、屏障完整性和功能性（通过细胞旁路和主动运输评估）没有改变。同时，微流体生物芯片中维持了 HepG2 C3A 细胞的活力和代谢。然后，作为概念验证，我们使用生物反应器来跟踪非那西丁通过肠道屏障的转运及其通过 HepG2 C3A 细胞的 CYP1A 代谢为扑热息痛。我们的结果证明了与静态共培养对照相比，该生物反应器与细胞共培养的性能，在静态共培养对照中检测到弱生物转化为扑热息痛。我们的研究表明，这种生物反应器将细胞培养屏障和肝脏微流体培养的优点结合在体外研究的共同框架中。 (C) 2014 Elsevier Ltd. 保留所有权利。
We developed a new biological model to mimic the organ organ interactions between the intestine and the liver. We coupled polycarbonate cell culture inserts and microfluidic biochips in an integrated fluidic platform allowing dynamic co-cultures (called IIDMP for Integrated Insert in a Dynamic Microfluidic Platform). The intestinal compartment was simulated using Caco-2 TC7 cells and the liver one by HepG2 C3A. We showed that Caco-2 TC7 viability, barrier integrity and functionality (assessed by paracellular and active transport), were not altered during co-cultures in the bioreactor in comparison with the conventional insert Petri cultures. In parallel, the viability and metabolism of the HepG2 C3A cells were maintained in the microfluidic biochips. Then, as proof of concept, we used the bioreactor to follow the transport of phenacetin through the intestinal barrier and its metabolism into paracetamol by the CYP1A of the HepG2 C3A cells. Our results demonstrated the performance of this bioreactor with cell co-cultures compared to static co-culture controls in which weak biotransformation into paracetamol was detected. Our study illustrated the interest of such a bioreactor combining the advantages of a cell culture barrier and of liver microfluidic cultures in a common framework for in vitro studies. (C) 2014 Elsevier Ltd. All rights reserved.