Table 2.

Glioma organoid models.

Cancer Type	Source of Organoids	Culture Technique	Endpoint of Study	Resemblance to Parent Tumor	References
Glioblastoma	Patient-derived glioma stem cells	1. Co-culture of GSCs and iPSCs 2. Supplementing GSCs with normal cerebral organoids 3. Fusion of GSC spheres with normal brain organoids	Three techniques to model GSC invasion in normal brain organoids and creation of GBM organoids	No direct comparison to primary tissue could be made.	Goranci-Buzhala et al. (2020) [83]
	Patient-derived glioblastoma and non-glioblastoma stem cells	Matrigel + culture shaking in NBM complete media	Spatial distribution of GBM replicated in organoids derived from glioblastoma and non-glioblastoma stem cells	Orthotopically implanted PDOs were diffuse and infiltrative, histologically resembling the parent tumor.	Hubert et al. (2016) [57]
	Human embryonic stem cells	Normal cerebral organoids co-cultured with patient-derived tumor cells or oncogene introduction through electroporation	Normal human-derived cerebral organoids a vector for glioblastoma organoid modeling	Engineered PDOs displayed a mesenchymal phenotype consistent with patient-derived GBMs on transcriptomic analysis.	Ogawa et al. (2018) [56]
	Human glioblastoma tissue	Patient tissue parcellated and cultured without an extracellular matrix	Glioblastoma organoid protocol development from primary tissue samples with minimum processing	PDOs had cellular and nuclear atypia, abundant mitotic figures, and pleomorphic nuclei consistent with high-grade parent tumors on histologic analysis.	Jacob et al. (2020) [62]
	Glioblastoma spheroids infiltrating cerebral organoids	Co-culture of mouse early (6-day-old) cerebral organoids with glioblastoma spheroids created from glioblastoma stem cell culture	Demonstration of hybrid glioblastoma organoid modeling	Co-cultured organoids displayed core infiltration and expression of GBM stem cell markers NESTIN and SOX2.	Da Silva et al. (2018) [82]
	Patient-derived glioma stem cells	Co-culture of cerebral organoids with transduced GSCs on NBM	Single-cell RNA sequencing comparison of four patient-derived glioblastoma models	Organoids displayed microscopic invasion and single-cell heterogeneity consistent with parent tumors.	Pine et al. (2020) [85]
Central nervous system primitive neuroectodermal-like and glioblastoma-like tumor	Human embryonic stem cells	Neoplastic cerebral organoids (Neo-COR); combination of plasmids introduced into normal cerebral organoids through electroporation before te organoids embedded in Matrigel	Demonstration of brain tumorigenesis through introduction of oncogenic mutations in normal cerebral organoids through transposon and CRISPR/Cas9 mutagenesis	GBM-like Neo-COR displayed upregulation of GBM genes on transcriptomic analysis.	Bian et al. (2018) [68]

Abbreviations: GBM, glioblastoma; GSCs, glioma stem-like cells; NBM, neurobasal medium.