文献类型：期刊文献

英文题名：Microfluidic co-culture of liver tumor spheroids with stellate cells for the investigation of drug resistance and intercellular interactions

作者：Chen, Yuqing[1];Sun, Wei[1];Kang, Lu[1];Wang, Yuerong[1];Zhang, Min[2];Zhang, Hongyang[1];Hu, Ping[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design & Modern Engn Ct, Sch Pharm, Shanghai 200237, Peoples R China

年份：2019

卷号：144

期号：14

起止页码：4233

外文期刊名：ANALYST

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000474643700008)】；

基金：This research was supported financially by the National Natural Science Foundation of China (No. 81573397). JS-1 cells were provided by Professor Xiaoning Wang, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine.

语种：英文

摘要：Hepatic stellate cells (HSCs), a major component of the tumor microenvironment in liver cancer, play important roles in cancer progression as well as drug resistance. Here, we presented a microchannel plate-based co-culture model that integrated Hepa1-6 tumor spheroids with JS-1 stellate cells in three-dimensional (3D) concave microwells to mimic the in vivo tumor microenvironment by recapitulating epithelial-mesenchymal transition and chemoresistance. The expression of epithelial-mesenchymal transition (EMT)-related markers and factors was analyzed using immunofluorescent staining and the changes in viability following exposure to different concentrations of paclitaxel were measured. Cell spheroids formed 3D tumor spheroids within 3 days. Culture conditions were optimized for Hepa1-6 cells and JS-1 cells, and their appropriate interactions were confirmed by reciprocal activation. JS-1 under co-culture showed a change in cellular morphology and an increased expression of alpha-SMA. The expression of EMT-related markers, such as vimentin and TGF-beta 1, was higher in the co-cultured Hepa1-6 spheroids compared to that in mono-cultured spheroids. Following paclitaxel exposure, JS-1 cells showed significant changes in survival under both mono- and co-culture conditions, while Hepa1-6 presented negligible changes. The proposed microfluidic platform makes it possible to observe the positioned three-dimensional cell spheroids, which would be extensively used not only for well-organized spheroid creation, but also for better quantitative and qualitative understanding of the cell-cell interaction effect.