63145 20200324135213.0 doi 10.1038/s41598-017-12049-4 sideral 101469 ART-2017-101469 eng (orcid)0000-0003-3660-8651 Virumbrales-Muñoz, Maria Universidad de Zaragoza Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models 2017 Access copy available to the general public Unrestricted The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation. info:eu-repo/grantAgreement/ES/MICINN/MTM2012-31073 info:eu-repo/grantAgreement/ES/MINECO/DPI2011-28262-C04-01 info:eu-repo/grantAgreement/ES/MINECO/DPI2015-65401-C3-1-R info:eu-repo/grantAgreement/ES/MINECO/MAT2015-69967-C3-1 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.122 2017 MULTIDISCIPLINARY SCIENCES 12 / 64 = 0.188 2017 Q1 T1 1.533 2017 Multidisciplinary 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ayuso, Jose María Olave, Marta (orcid)0000-0003-0734-129X Monge, Rosa de Miguel, Diego (orcid)0000-0003-3043-147X Martinez-Lostao, Luis Universidad de Zaragoza Le Gac, Séverine (orcid)0000-0001-8741-6452 Doblaré, Manuel Universidad de Zaragoza (orcid)0000-0003-2410-5678 Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0001-5376-4440 Fernández, Luis Universidad de Zaragoza 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 7, 1 (2017), 11998 [15 pp] Sci. rep. SCIENTIFIC REPORTS 2045-2322 4700077 http://zaguan.unizar.es/record/63145/files/texto_completo.pdf Versión publicada 107982 http://zaguan.unizar.es/record/63145/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:63145 articulos driver 2020-03-24-10:01:16 ARTICLE