Table 1

Summary of characteristics of different GBM models

GBM model	Cell resource	Culture condition	Characteristics	Advantages and disadvantages	References
2-D model	Patient-derived GBM cells	DMEM or DMEM/F12 culture medium with 10% FBS	Monolayer adherent cells	Easy cultivation, lack of stemness and differentiation ability	^7,8
				Sensitivity to therapy and radiation	¹⁰
3-D model	Established cell line	DMEM/F12 medium without serum, supplemented with EGF and bFGF	Tumor balls	Stemness, self-renewal, and differentiation ability; slow proliferation	^7–9
				Enhanced heterogeneity and drug resistance	^11,12
GBO	iPS cells	DMEM/F12 containing B27, N2, and bFGF	Brain tissue organoid	Characteristics of human brain development	^1,13
	GBM cell line		Matrix-free	High stemness and strong cell-cell interaction	¹⁵
Genetically manipulated cerebral organoids	iPS cells	DMEM/F12 containing B27, N2, and bFGF	Applied CRISPR/Cas9 technology	Observation of the earliest steps of tumorigenesis in a human context with a defined genetic manipulation	^17–19
			Organoids derived from patients with c-Met mutation	Accelerated differentiation into neurons for c-Met iPSC-A compared with control iPSC-A	²⁰
PDO	Patient tumor tissue	DMEM/F12 containing B27, N2, and bFGF	Organoids derived directly from glioblastoma specimens	Generation of gradients of stem cell density and hypoxia with PDOs	²²
		DMEM/F12, Neurobasal medium, 1× GlutaMAX, NEAAs, penicillin–streptomycin, N2, and B27	Preservation of key characteristics and gene expression of the parental tumors	Fast, recapitulation of heterogeneity and key features of glioblastomas	^23–25
		5% (w/v) GelMA and 0.25% (w/v) HA as the ECM	Application of GelMA–HA hydrogels	Maintenance of parental tumor features, such as the expression of key genes	²⁶
		DMEM, FBS, UltraGlutamine I, penicillin–streptomycin, and NEAA	Description of specific steps	High success rate and favorable preservation of patient heterogeneity	^27,28
			Analysis of genetic characteristics of parental patients and PDO models	Mimicking of the tumor microenvironment and angiogenesis; high-throughput drug screening for precision medicine	^29,30
GLICO	mESCs and GSCs	mESCs: DMEM-HG, KRS, MEM-NEAA, glutamine, β-mercaptoethanol, and LIF GSCs: Neurobasal medium, B27, N2, bFGF, and EGF	GBM spheroids in coculture with mouse embryonic stem cell (mESC)–derived early-stage cerebral organoids (eCOs)	Favorable simulation of organoid compartments and infiltration patterns	³¹
	GSCs and hESCs	GSCs: Neurobasal medium, B27, N2, bFGF, and FGF Cerebral organoids: DMEM/F12, Neurobasal medium, N2, B27, insulin, GlutaMAX, and MEM-NEAA	GSCs co-cultured with cerebral organoids	Simulation of invasion patterns and chemoradiotherapy resistance of patients with GBM	^10,32
	iPSCs and GSCs	GSCs: Neurobasal medium, B27, L-Glutamine, Heparin, bFGF, and EGF iPSCs: DMEM/F12 GlutaMAX, N2, B27, insulin, and L-glutamine		Characterization of GBM invasion into human brain at a quantitative or transcriptional level	³³
3-D printed GBO	GBM cells, ECM, and HUVECs	GBM cells: DMEM, FBS, and penicillin–streptomycin HUVECs: endothelial cell growth medium 2	GBOs reconstructed from patient-derived glioma cells, vascular endothelial cells, and extracellular matrix, on the basis of 3-D printing technology	Recapitulation of the structural, biochemical, and biophysical properties of native tumors; reproduction of clinically observed patient-specific resistance to treatment	^37,38
	GBM cells, monocytes, GASCs, and microglia	GBM cells and monocytes: MEM, FBS, L-glutamine, and NEAA GASCs: DMEM-HG medium Microglia: microglia complete medium with serum	Use of bioinks based on modified alginate to prepare tumor models incorporating tumor and stromal cells from glioblastoma	Spatial organization of multiple cell types and recovery of protein and RNA at the single cell level	³⁹
	GSCs, macrophages, astrocytes, and neural stem cells	GSCs: Neurobasal medium, B27, L-glutamine, bFGF, and FGF Monocytes: RPMI 1640 medium, and FBS Neural stem cells: complete NBM medium for GSCs Astrocytes: astrocyte medium	Model comprising patient-derived GSCs, macrophages, astrocytes, and neural stem cells in HA-rich hydrogel	Recapitulation of glioblastoma transcriptional profiles; promotion of hypoxic and invasive signatures; platform for drug response modeling	^42,43