期刊
MATERIALS TODAY BIO
卷 15, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mtbio.2022.100274
关键词
Extracellular matrix; Lung; Decellularization; Cancer cell; Drug screening
资金
- China Postdoctoral Science Foundation [2018M643504]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2018HXBH041]
The study demonstrates that ECM derived from decellularization of native porcine lungs provides better support for cell adhesion, distribution, viability, and proliferation. The optimal diameter for micropattern arrays is 100-150 μm.
Aims: This study aims to evaluate ECM-coated micropattern arrays derived from decellularization of native porcine lungs as a novel three-dimensional cell culture platform.Methods: ECM derived from decellularization of native porcine lungs was exploited to prepare hydrogels. Then, dECM-coated micropattern arrays were fabricated at four different diameters (50, 100, 150 and 200 mu m) using polydimethylsiloxane (PDMS). Two lung cancer cell lines, A549 and H1299, were tested on a dECM-coated micropattern array as a novel culture platform for cell adhesion, distribution, proliferation, viability, pheno-type expression, and drug screening to evaluate the cytotoxicity of paclitaxel, doxorubicin and cisplatin.Results: The ECM derived from decellularization of native porcine lungs supported cell adhesion, distribution, viability and proliferation better than collagen I and Matrigel as the coated matrix on the surface. Moreover, the optimal diameter of the micropattern arrays was 100-150 mu m, as determined by measuring the morphology, viability, proliferation and phenotype of the cancer cell spheroids. Cell spheroids of A549 and H1299 on dECM-coated micropattern arrays showed chemoresistance to anticancer drugs compared to that of the monolayer. The different distributions of HIF-1 alpha, MCL-1 (in the center) and Ki-67 and MRP2 (in the periphery) of the spheroids demonstrated the good establishment of basal-lateral polarity and explained the chemoresistance phenomenon of spheroids.Conclusions: This novel three-dimensional cell culture platform is stable and reliable for anticancer drug testing. Drug screening in dECM-coated micropattern arrays provides a powerful alternative to existing methods for drug testing and metabolic profiling in the drug discovery process.
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