Preclinical Models of Low-Grade Gliomas
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Diffuse Low-Grade Gliomas
1.2. Grading and Classification of Gliomas
1.3. Molecular Pathology of Low-Grade Gliomas
1.4. IDH-Mutant Astrocytoma
1.5. IDH-Mutant Oligodendroglioma
1.6. Ideal Preclinical Model of Low-Grade Gliomas
2. Cell Culture Models
2.1. Murine Cell Lines
2.2. Patient-Derived Cell Lines
3. Murine Models
3.1. Murine-Derived Genetically Engineered Mouse Models
3.2. Patient-Derived Xenograft Models
4. Emerging Models
4.1. Patient Avatars of Low-Grade Gliomas
4.2. The Promise of In Silico Models
5. Challenges and Strategies in the Development of Low-Grade Glioma Models
5.1. IDH Status
5.2. Immune Microenvironment
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Viral or Nonviral | Vector Type | Advantage | Limitations | Example |
---|---|---|---|---|
Viral | Retrovirus | Cell-specific infection | Safety concerns when transducing oncogenes | [48,59,60] |
Viral | Lentivirus | Infects both dividing and nondividing cells | Safety concerns when transducing oncogenes | [61,62] |
Viral | Adenovirus | No genome integration | High immunogenicity | [63] |
Nonviral | Nonviral transposon (Sleeping Beauty) | Suitable for discovery of tumor drivers | Genome integration may disrupt gene expression | [64] |
Model Category | Specific Model | Genes Involved | Genetic Heterogeneity | Immunocompetent | Brain Micro-Environment | Blood–Brain Barrier | Reproducible |
---|---|---|---|---|---|---|---|
Murine cell line | ENU-induced murine tumor cells | BRAF, TP53, PDGFRa, CDKN2a, EGFR, and no IDH | yes | no | no | no | no |
Murine cell line | IDH1 mutant expression in SVC cells | IDH | no | no | no | no | yes |
Patient-derived cell line | BT142 | IDH | no | no | no | no | yes |
Patient-derived cell line | TS603 | IDH, 1p/19q codeletion | no | no | no | no | yes |
Murine-derived GEMMs | Sleeping Beauty transposase system | IDH, TP53, and ATRX | no | yes | yes | yes | yes |
Murine-derived GEMMs | RCAS-mutIDH-PDGFA-CDKN2A-ATRX-PTEN | IDH, CDKN2a, ATRX, PTEN, and PDGFA | no | yes | yes | yes | yes |
Murine derived GEMMs | RCAS-mutIDH-PDGF driven-p53 knockdown | IDH, PDGF, and TP53 | no | yes | yes | yes | yes |
Patient-derived murine model | Various LGG orthotopic xenografts | IDH, FUBP1, and CIC | partially | no | partially | yes | yes |
Genetically modified neurosphere | hESCs with lentiviral modification | IDH, TP53, and ATRX | no | no | no | no | yes |
Mouse to mouse xenograft | PDGF-B overexpressing mouse NSC into mouse brain | PDGF-B | partially | yes | yes | yes | yes |
iPSC | human LGG iPSC | IDH | partially | no | no | no | yes |
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Dasgupta, P.; Balasubramanyian, V.; de Groot, J.F.; Majd, N.K. Preclinical Models of Low-Grade Gliomas. Cancers 2023, 15, 596. https://doi.org/10.3390/cancers15030596
Dasgupta P, Balasubramanyian V, de Groot JF, Majd NK. Preclinical Models of Low-Grade Gliomas. Cancers. 2023; 15(3):596. https://doi.org/10.3390/cancers15030596
Chicago/Turabian StyleDasgupta, Pushan, Veerakumar Balasubramanyian, John F. de Groot, and Nazanin K. Majd. 2023. "Preclinical Models of Low-Grade Gliomas" Cancers 15, no. 3: 596. https://doi.org/10.3390/cancers15030596