Table 3.
Model | Methodology | Pro | Con | Cell lines/models | References |
---|---|---|---|---|---|
ENU-induced | • Exposure in utero to ENU (DNA damage induces brain tumors embryos); • Dissection and culturing of these tumors in vitro to create animal GB models. |
• Immunotherapeutic research tool. • Commercially available. • Extensively studied. • Provides genetic brain heterogeneity, micro-environment • Intact immune system and BBB. |
• Often ENU tumor characteristic differs from human GB; • GB tumor formation poorly reproducible. |
C6, 9L, T9, RG2, F98, BT4C, and RT-2 | 278,283,498-504 |
GEMM | • Gene mutations result in spontaneous tumor formation; • Transgenic mouse lines are commonly derived by direct pronuclear microinjection of transgenes into fertilized oocytes, followed by implantation into pseudo-pregnant females; • Gene targeting of embryonic stem cells by electroporation; • Viral-mediated methods; • Cre recombinase transgenics |
• Close genetic resemblance to human GB tumors: suitable to investigate behavior of genetically defined gliomas. • Identify the molecular events responsible for tumor initiation and progression. • Analyze the role of the microenvironment • Studies on drug distribution to glioma cells in the brain. |
• Does not completely reflect the intratumoral genomic and phenotypic heterogeneity; • Tumor initiation cannot be controlled. |
EGFR amplification/Ras-gene activation (classical GB); NF1 depletion (mesenchymal GB); PDGF amplification (proneural GB) | 276,278,279,284,504-506 |
PDX | • Surgically obtained human glioma specimens. After preparing cell/tissue cultures these can also be implanted heterotopically or orthotopically in immunocompromised rodents; • Immediate implantation of surgically obtained material into the brain of the animal |
• Recapitulate genetic and phenotypic features of the original tumor | • Relatively low engraftment and variable growth rate hamper standardization and experimental planning. • Requires immunodeficient animals. |
IDH1R132H-E478 | 276,285,504 |
PDGC | • High engraftment and growth rates; • Good reproducibility; • Reliable disease growth and progression |
• Does not recapitulate genetic and phenotypical features of original tumor. • Requires immunodeficient animals |
U87, and U251 |
Footnotes and abbreviated content: Ethyl-nitrosourea (ENU)-induced gliomas, genetically engineered models (GEMM) and patient-derived xenograft or glioma cell models (PDX or PDGC), platelet-derived growth factor (PDGF), blood brain barrier (BBB), glioblastoma (GB), neurofibromatosis type 1 gene (NF1), epidermal growth factor receptor (EGFR), deoxyribonucleic acid (DNA).