Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device
Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device
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DOI：
10.1016/j.jbiosc.2013.11.019
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发表时间：
2014-06-01
影响因子：
2.8
通讯作者：
Sakai, Yasuyuki
中科院分区：
文献类型：
--
作者：
Nakayama, Hidenari;Kimura, Hiroshi;Sakai, Yasuyuki
我们最近开发了一种基于聚二甲基硅氧烷（PDMS）的三室微流体共培养装置，使不同细胞群的实时相互作用成为一种先进的生理相关的基于细胞的测定。该装置具有阀门和基于小型磁力搅拌器的内部泵，用于简单灵活的灌注操作。在本研究中，我们应用该装置评价伊立替康（CPT-11）对肺的毒性，因为其可通过肝脏解毒并在人体脂肪中蓄积。我们成功地培养了代表性的三种不同的组织模型细胞在每个隔室在个别的培养条件下，也在整个灌注。在各种共培养条件下，在存在和不存在由小鼠成纤维细胞系313-L1诱导的原代大鼠肝细胞（肝组织模型）和脂肪细胞样细胞（脂肪组织模型）的情况下，当给予50 μ M CPT-11时，测量大鼠肺上皮细胞系L-2的生长抑制。尽管CPT-11在灌注培养72小时后对装置中的L-2细胞的纯培养物显示出中等毒性，但这主要在肝组织存在下降低。L-2细胞生长的抑制与从每个隔室中基于荧光图像的分析获得的曲线下面积（AUC）值一致。这些结果表明，开发的简单和灵活的微流控共培养装置，与适当的基于图像的分析，可用于评价药物候选物的毒代动力学行为在全身水平。(C)2013年，生物技术学会，日本。All rights reserved.
We recently developed a polydimethylsiloxane (PDMS)-based three-compartment microfluidic cocultivation device enabling real-time interactions of different cell populations as an advanced physiologically-relevant cell-based assay. This device had valves and small magnetic stirrer-based internal pumps for easy and flexible perfusion operations. In this study, we applied this device for the evaluation of Irinotecan (CPT-11) toxicity to the lung, because it is detoxified by the liver and accumulated in the fat in humans. We successfully cultured representative three different tissue model cells in each compartment under the individual culture conditions and also in entire perfusion. Growth inhibition of rat lung epithelial cell line L-2, was measured when administered with 50 mu M CPT-11 under various cocultivation conditions with respect to the presences and absence of primary rat hepatocytes (liver tissue model) and adipocyte-like cells (fat tissue model) induced from a mouse fibroblast cell line, 313-Ll. Although CPT-11 showed moderate toxicity to the pure culture of L-2 cells in the device after 72 h of perfusion culture, this was lowered mainly in the presence of the liver tissue. Inhibition of the L-2 cell growth agreed with the area under curve (AUC) values obtained from fluorescent image-based analyses in each compartment. These results demonstrate that developed simple and flexible microfluidic cocultivation device, with appropriate image-based analyses, can be used in evaluating toxicokinetic behaviors of drug candidates in systemic levels. (C) 2013, The Society for Biotechnology, japan. All rights reserved.