000058491 001__ 58491
000058491 005__ 20170117133943.0
000058491 0247_ $$2doi$$a10.1093/neuonc/now230
000058491 0248_ $$2sideral$$a97342
000058491 037__ $$aART-2017-97342
000058491 041__ $$aeng
000058491 100__ $$0(orcid)0000-0002-9414-1845$$aAyuso Domínguez, José María
000058491 245__ $$aGlioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events
000058491 260__ $$c2017
000058491 5060_ $$aAccess copy available to the general public$$fUnrestricted
000058491 5203_ $$aBackground: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These “waves” of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM’s spread and invasion, the recreation of these structures in vitro has remained challenging.
Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease.
Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon.
Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution.
000058491 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BES-2012-059940$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2011-28262-C04-01$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2015-65401-C3-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/MTM2015-71200-R
000058491 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000058491 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000058491 700__ $$0(orcid)0000-0003-0734-129X$$aMonge Prieto, Rosa María
000058491 700__ $$aMartinez-Gonzalez, Alicia
000058491 700__ $$0(orcid)0000-0003-3660-8651$$aVirumbrales Muñoz, Maria$$uUniversidad de Zaragoza
000058491 700__ $$aLlamazares Prieto, Guillermo Alejandro
000058491 700__ $$aBerganzo, Javier
000058491 700__ $$aHernandez-Lain, Aurelio
000058491 700__ $$aSantolaria, Jorge
000058491 700__ $$0(orcid)0000-0001-8741-6452$$aDoblaré Castellano, Manuel$$uUniversidad de Zaragoza
000058491 700__ $$aHubert, Christopher
000058491 700__ $$aRich, Jeremy N.
000058491 700__ $$aSanchez-Gomez, Pilar
000058491 700__ $$aPerez-Garcia, Victor M.
000058491 700__ $$0(orcid)0000-0003-2410-5678$$aOchoa Garrido, Ignacio$$uUniversidad de Zaragoza
000058491 700__ $$0(orcid)0000-0001-5376-4440$$aFernández Ledesma, Luis José$$uUniversidad de Zaragoza
000058491 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDepartamento de Anatomía e Histología Humanas$$cHistología
000058491 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular
000058491 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDepartamento de Ingeniería Mecánica$$cMec. de Medios Contínuos y Teor. de Estructuras
000058491 773__ $$g(2017), [11 pp.]$$pNeuro-oncology$$tNEURO-ONCOLOGY$$x1522-8517
000058491 8564_ $$s1776376$$uhttp://zaguan.unizar.es/record/58491/files/texto_completo.pdf$$yPostprint
000058491 8564_ $$s77567$$uhttp://zaguan.unizar.es/record/58491/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000058491 909CO $$ooai:zaguan.unizar.es:58491$$particulos$$pdriver
000058491 951__ $$a2017-01-16-14:16:14
000058491 980__ $$aARTICLE