A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity
Open accessAbstract
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.
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T cells are decreased in 9/10 of the cultured GBOs.
“We observed that T cells are decreased in 9/10 of the cultured GBOs (Figure S3H), consistent with the original report.5”
From Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy (2025) · cites this paper as [5]
The Results section on molecular heterogeneity reports downregulation of immune-related genes in cultured GBOs, and the Discussion describes declining resident immune-cell abundance over time. Those findings are consistent with the citing authors’ observation, but our copy does not report a specific decrease in T cells; the 9/10 figure is the citing authors’ own result, not a figure attributed to this source. Page numbers are unavailable in our copy. (LLM, conf=0.81)
Experimental — accuracy not yet measuredLiving biobanks can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases.
“‘living biobanks’ can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers124,151,176–178, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases179”
From Human disease models in drug development (2023) · cites this paper as [178]
Several patient-derived organoid models have been developed for primary brain tumors, mostly for GBM.
“Several patient-derived orga- noid models have been developed for primary brain tumors, mostly for GBM.5–9”
From Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy (2025) · cites this paper as [5]
The GBO model and the PDE model culture tumor explant without or with Matrigel, respectively.
“The patient-derived GBM or- ganoid (GBO) model5 and patient-derived explants (PDEs) model7 culture tumor explant without or with Matrigel, respec- tively.”
From Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy (2025) · cites this paper as [5]
There is no significant difference in the distance between IPTO and GBO, but the GBO data are limited by a low quantity and significant variability.
“We also compared IPTO data with the GBO results5; there is no significant difference in the distance between IPTO and GBO but the GBO data are limited by a low quantity and significant variability (Figure 4F).”
From Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy (2025) · cites this paper as [5]
PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC.
“PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC18,19,48–50.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [48]
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Human organoids: model systems for human biology and medicine
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Patient-derived organoids as a predictive biomarker for treatment response in cancer patients
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Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease
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An Automated Organoid Platform with Inter-organoid Homogeneity and Inter-patient Heterogeneity
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Applications of organoids for cancer biology and precision medicine
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The Many Facets of Therapy Resistance and Tumor Recurrence in Glioblastoma
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Organoids to model liver disease
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Tumor organoid models in precision medicine and investigating cancer-stromal interactions
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Cancer research using organoid technology
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In Vitro Strategies to Vascularize 3D Physiologically Relevant Models
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3d organ-on-a-chip: the convergence of microphysiological systems and organoids
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“Organoids are now considered as avatars in personalized medicine (Seidlitz et al., 2018; Frappart et al., 2020; Jacob et al., 2020; Jian et al., 2020; Saltsman et al., 2020; Shi et al., 2020; Witte et al., 2020; Bi et al., 2021; Kazama et al., 2021; Grossman et al., 2022) with the potential to contribute to reducing t…”
BackgroundPeng, T., Ma, X., Hua, W., Wang, C., Chu, Y., Sun, M., Fermi, V., Hamelmann, S., Lindner, K., Shao, C., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.01.002 · Cited by 86 · see citing works
Present Application and Perspectives of Organoid Imaging Technology
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Organoid co‐culture models of the tumor microenvironment promote precision medicine
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“Biobanking, as samples obtained from patients can be used to generate patient-derived organoids (PDOs) and stored as a resource for future research (Takebe et al., 2018; Jacob et al., 2020); 5.”
Background<i>In vitro</i> functional models for human liver diseases and drug screening: beyond animal testing
Paradiso, A., Volpi, M., Rinoldi, C., Celikkin, N., Contessi Negrini, N., Bilgen, M., Dallera, G., Pierini, F., Costantini, M., Święszkowski, W., et al. (2023) · Biomaterials Science · doi:10.1039/d1bm01872h · Cited by 40 · see citing works
Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution
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Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry
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Gut microbiota dysbiosis induced by brain tumors modulates the efficacy of immunotherapy
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- Authors
- Jacob, F., Salinas, R. D., Zhang, D. Y., Nguyen, P. T. T., Schnoll, J. G., Wong, S. Z. H., Thokala, R., Sheikh, S., Saxena, D., Prokop, S., Liu, D.-A., Qian, X., Petrov, D., Lucas, T., Chen, H. I., Dorsey, J. F., Christian, K. M., Binder, Z. A., Nasrallah, M., Brem, S., O’Rourke, D. M., Ming, G.-L., & Song, H.
- Affiliations
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- Philadelphia VA Medical Center (US)
- Abramson Cancer Center (US)
- Corresponding author
- O’Rourke, Donald M.
- Ming, Guo-li
- Song, Hongjun
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 180
- Issue
- 1
- Pages
- 188-204.e22
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7556703
- OpenAlex
- W2997979341
- Cited by
- 1,149
- References
- 94
- Citations by year
- 2026: 178 · 2025: 211 · 2024: 237 · 2023: 146 · 2022: 153 · 2021: 146 · 2020: 77 · 2019: 1
- FWCI
- 52.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- glioblastoma, patient-derived organoids, tumor heterogeneity, mutational landscape, drug susceptibility testing, personalized treatment, CAR T-cell therapy, tumor infiltration, xenograft transplantation, in vitro tumor model
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Female, Glioblastoma, Humans, Male, Mice, Nude, Middle Aged, Models, Biological, Organoids, Reproducibility of Results, Biological Specimen Banks, Cell Culture Techniques, Xenograft Model Antitumor Assays, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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