Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events

Ayuso, Jose María ; Monge, Rosa ; Martinez-Gonzalez, Alicia ; Virumbrales-Munoz, Maria (Universidad de Zaragoza) ; Llamazares, Guillermo A. ; Berganzo, Javier ; Hernandez-Lain, Aurelio ; Santolaria, Jorge (Universidad de Zaragoza) ; Doblare, Manuel (Universidad de Zaragoza) ; Hubert, Christopher ; Rich, Jeremy N. ; Sanchez-Gomez, Pilar ; Perez-Garcia, Victor M. ; Ochoa, Ignacio (Universidad de Zaragoza) ; Fernandez, Luis J. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1093/neuonc/now230

Año: 2017

Publicado en: NEURO-ONCOLOGY 19, 4 (2017), 503-513
ISSN: 1522-8517

Factor impacto JCR: 9.384 (2017)

Categ. JCR: ONCOLOGY rank: 15 / 223 = 0.067 (2017) - Q1 - T1
Categ. JCR: CLINICAL NEUROLOGY rank: 9 / 197 = 0.046 (2017) - Q1 - T1

Factor impacto SCIMAGO: 4.064 - Cancer Research (Q1) - Oncology (Q1) - Neurology (clinical) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2012-059940
Financiación: info:eu-repo/grantAgreement/ES/MINECO/DPI2011-28262-C04-01
Financiación: info:eu-repo/grantAgreement/ES/MINECO/DPI2015-65401-C3-1-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/MTM2015-71200-R

Tipo y forma: Article (PostPrint)

Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Ing. Procesos Fabricación (Dpto. Ingeniería Diseño Fabri.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)