Cell
Volume 180, Issue 1, 9 January 2020, Pages 188-204.e22
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A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity

https://doi.org/10.1016/j.cell.2019.11.036Get rights and content
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Highlights

  • Rapid establishment of glioblastoma organoids (GBOs) in a defined medium with biobank

  • GBOs maintain parental tumor cellular heterogeneity, gene expression, and mutations

  • GBO transplantation exhibits efficient engraftment and aggressive infiltration

  • Tumor-specific treatment responses in GBOs to drugs and CAR-T cells

Summary

Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.

Keywords

glioblastoma
Organoid
biobank
tumor heterogeneity
personalized therapies
xenograft
drug testing
CAR-T cells
translational
cancer modeling

Cited by (0)

17

The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

18

Present address: Department of Pathology, University of Florida, Gainesville, FL 32610, USA

19

These authors contributed equally

20

Lead Contact