Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

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Authors

FEDOROVÁ Veronika POSPÍŠILOVÁ Veronika VÁŇOVÁ Tereza AMRUZ ČERNÁ Kateřina ABAFFY Pavel SEDMÍK Jiří RAŠKA Jan VOCHYÁNOVÁ Simona MATŮŠOVÁ Zuzana HOUSEROVÁ Jana VALIHRACH Lukáš HODNÝ Zdeněk BOHAČIAKOVÁ Dáša

Year of publication 2023
Type Article in Periodical
Magazine / Source MOLECULAR ONCOLOGY
MU Faculty or unit

Faculty of Medicine

Citation
Web https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13389
Doi http://dx.doi.org/10.1002/1878-0261.13389
Keywords cerebral organoids; GLICO; glioblastoma; induced pluripotent stem cells
Description It is currently challenging to adequately model the growth and migration of glioblastoma using two-dimensional (2D) in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity. However, with the advent of three-dimensional (3D) cell cultures and human-induced pluripotent stem cell (iPSC)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-CO (GLICO) coculture model helps to preserve the phenotype of the patient-specific tissue. Here, we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of cocultured glioblastoma. Our data demonstrate that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model. Lastly, we show that this coculture model (and the human brain-like microenvironment) can significantly transform the gene expression profile of the established U87 glioblastoma cell line into proneural and classical glioblastoma cell types.
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