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Three-dimensional model of glioblastoma by co-culturing tumor stem cells with human brain organoids

Azzarelli, Roberta; Ori, Michela; Philpott, Anna; Simons, Benjamin D; (2021) Three-dimensional model of glioblastoma by co-culturing tumor stem cells with human brain organoids. Biology Open , 10 (2) , Article bio056416. 10.1242/bio.056416. Green open access

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Abstract

Emerging three-dimensional (3D) cultures of glioblastoma are becoming powerful models to study glioblastoma stem cell behavior and the impact of cell-cell and cell-microenvironment interactions on tumor growth and invasion. Here we describe a method for culturing human glioblastoma stemcells (GSCs) in 3D by co-culturing them with pluripotent stem cell-derived brain organoids. This requires multiple coordinated steps, including the generation of cerebral organoids, and the growth and fluorescence tagging of GSCs. We highlight how to recognize optimal organoid generation and how to efficiently mark GSCs, before describing optimized co-culture conditions. We show that GSCs can efficiently integrate into brain organoids and maintain a significant degree of cell fate heterogeneity, paving the way for the analysis of GSC fate behavior and lineage progression. These results establish the 3D culture system as a viable and versatile GBM model for investigating tumor cell biology and GSC heterogeneity.

Type: Article
Title: Three-dimensional model of glioblastoma by co-culturing tumor stem cells with human brain organoids
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/bio.056416
Publisher version: http://dx.doi.org/10.1242/bio.056416
Language: English
Additional information: © 2021. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Neural stem cells, Glioblastoma, Organoid, Neurogenesis, 3D culture, Brain tumor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10189165
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