58491 20200324135213.0 doi 10.1093/neuonc/now230 sideral 97342 ART-2017-97342 eng (orcid)0000-0002-9414-1845 Ayuso, Jose María Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events 2017 Access copy available to the general public Unrestricted Background: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These “waves” of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM’s spread and invasion, the recreation of these structures in vitro has remained challenging. Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease. Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon. Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution. info:eu-repo/grantAgreement/ES/MINECO/BES-2012-059940 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/MTM2015-71200-R info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 9.384 2017 ONCOLOGY 15 / 223 = 0.067 2017 Q1 T1 CLINICAL NEUROLOGY 9 / 197 = 0.046 2017 Q1 T1 4.064 2017 Cancer Research 2017 Q1 Oncology 2017 Q1 Neurology (clinical) 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion (orcid)0000-0003-0734-129X Monge, Rosa Martinez-Gonzalez, Alicia (orcid)0000-0003-3660-8651 Virumbrales-Munoz, Maria Universidad de Zaragoza (orcid)0000-0002-5731-8840 Llamazares, Guillermo A. Berganzo, Javier Hernandez-Lain, Aurelio (orcid)0000-0001-7316-0003 Santolaria, Jorge Universidad de Zaragoza (orcid)0000-0001-8741-6452 Doblare, Manuel Universidad de Zaragoza Hubert, Christopher Rich, Jeremy N. Sanchez-Gomez, Pilar Perez-Garcia, Victor M. (orcid)0000-0003-2410-5678 Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0001-5376-4440 Fernandez, Luis J. Universidad de Zaragoza 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 5002 515 Universidad de Zaragoza Dpto. Ingeniería Diseño Fabri. Área Ing. Procesos Fabricación 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. 19, 4 (2017), 503-513 Neuro-oncology NEURO-ONCOLOGY 1522-8517 1776376 http://zaguan.unizar.es/record/58491/files/texto_completo.pdf Postprint 77567 http://zaguan.unizar.es/record/58491/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:58491 articulos driver 2020-03-24-10:01:05 ARTICLE