Table 2.

Comprehensive table with examples of most the published pre-clinical glioma models and their specifics over the last 30+ years

ModelOriginNameCharacteristicsCitations
Established cell lines Human GBM U87 High proliferation, non-diffuse, infiltrative patterns, widely used, well-characterized Clark et al. (2010), Allen et al. (2016)  
Established cell line Human GBM U251 High proliferation, necrotic regions, high Ki-67 positivity, maintains some tumor cell infiltrative patterns Torsvik et al. (2014), Li et al. (2017)  
Established cell line Human GBM T98G High ACTA2 expression, motility, minimally tumorigenic in mice Kiseleva et al. (2016), Rubenstein et al. (1999)  
Established cell line Human GBM A172 High proliferation Fenstermaker et al. (1998), Kiseleva et al. (2016)  
Established cell line Human GBM LN229 High proliferation, useful for studying MGMT methylation and drug response Beckner et al. (2005), Demircan et al. (2021)  
Established cell line Human GBM SF8628 H3.3K27M mutation, used in pediatric glioma studies Damanskienė et al. (2022), Olow et al. (2016)  
Established cell line Human GBM U373 High proliferation, widely used, well-characterized Dranoff et al. (1985), Takiguchi et al. (1985)  
Established cell line Human GBM SF9402 H3.3 wild type, used in combination therapy studies Hashizume et al. (2014), Wang et al. (2021)  
Established cell line Human GBM SF7761 H3.3K27M mutation, used in pediatric glioma studies Hashizume et al. (2012), Abe et al. (2020)  
Established cell line Human GBM GBM12 High proliferation, used in xenograft studies Sarkaria et al. (2006), Paraskevakou et al. (2007)  
Established cell line Human oligodendroglioma Hs683 High proliferation, useful for studying TMZ response Tasiou et al. (2001), Konduri et al. (2001)  
Established cell line Mouse GBM GL261 High MHC I, MHC II expression, RAS and p53 mutations. Widely used in immunotherapy studies Wu et al. (2008), Rappa et al. (2008)  
Established cell line Rat gliosarcoma 9L High proliferation, aggressive tumor growth in vivo Ghods et al. (2007), Kruse et al. (1994)  
Established cell line Rat GBM C6 High proliferation, aggressive tumor growth in vivo Giakoumettis et al. (2018), Kondo et al. (2004)  
3D models Human GBM GSCs Retains patient’s molecular subtypes Singh et al. (2004), Lee et al. (2006)  
3D models Human GBM PDOs Recapitulates inter- and intra-tumoral heterogeneity. Requires fresh tumor samples Chen et al. (2022), Jacob et al. (2020)  
3D models Human GBM GLICOs Allows for diffuse infiltration of glioma cells, mimicking human brain integration. Represents epigenomic-mediated transcriptomic states da Silva et al. (2018), Linkous et al. (2019)  
3D models Human GBM Cerebral organoids with CRISPR-Cas9 (GBM organoids) Genetically manipulated to develop oncogenic properties. Limited tumor heterogeneity Ogawa et al. (2018), Bian et al. (2018)  
3D models Human GBM Tumor organoids Represents hypoxic niches and oxygen gradients. Lack interactions with normal host brain cells Hubert et al. (2016), Heaster et al. (2019)  
3D models Human and rodent brain tissue Brain slice cultures (explants) Allows interaction with normal brain cells and ECM. Limited by the stress and eventual death of normal brain constituents Ohnishi et al. (1998), Eisemann et al. (2018)  
Oncogene induced syngeneic mouse models C57BL/6 mouse SB28 Poor immunogenic glioma model, commonly used in PD-L immunotherapy studies Letchuman et al. (2022), Murty et al. (2020)  
Chemically induced syngeneic mouse models C57BL/6 mouse GL261 High proliferation, aggressive tumor growth, mutation in KRAS. Genetic drift over time, limited representation of human gliomas, immunogenic. Szatmári et al. (2006), Daviaud et al. (2024)  
Chemically induced C57BL/6 mouse CT-2A Deficient in PTEN, necrotic, chemoresistant, undergoes unregulated angiogenesis. Used in immunotherapy studies limited genetic heterogeneity Riva et al. (2019), Casanova-Carvajal et al. (2019)  
Chemically induced C57BL/6 mouse GL26 High proliferation, mutation in KRAS, aggressive tumor growth, widely used Wouters et al. (2020), Kim et al. (2010)  
Spontaneous syngeneic models C3H mouse P560 High proliferation, aggressive tumor growth Kim et al. (2010), Bradford et al. (1986)  
GEMMs Neural progenitors or astrocytes Ink4a-Arf/Kras/Akt Model for studying cooperation between KRas activation and Ink4a-Arf loss in gliomagenesis Uhrbom et al. (2002), Figg et al. (2024)  
GEMMs Various glioma-initiating cells PTEN/p53/CDKN2/RB knockout Models high-grade astrocytomas with multiple genetic alterations Holland (2001), Alcantara Llaguno et al. (2019)  
GEMMs Neural stem/progenitor cells NF1/p53 Useful for studying NF1 and p53 interactions in gliomagenesis. Induces tumors that appear similar to astrocytomas Zhu et al. (2005), Liu et al. (2011)  
GEMMs Various glioma-initiating cells Idh1R132H Investigates metabolic vulnerabilities of IDH1 mutant gliomas. Demonstrates extreme vulnerability to NAD+ depletion Bardella et al. (2016), Zhang et al. (2019)  
GEMMs Various glioma-initiating cells CDKN2 Knockout/EGFR/PDGFR Studies cooperation between CDKN2 loss and growth factor signaling in gliomagenesis Zhu et al. (2009), Yeo et al. (2021)  
Xenograft models Human GBM U87MG xenograft High proliferation, circumscribed tumors. Widely used, good reproducibility. Lacks infiltrative pattern seen in human gliomas Mathieu et al. (2008), Donoghue et al. (2011)  
Cell line xenograft Human GBM U251 xenograft High proliferation, necrotic regions, well-characterized, widely used, limited heterogeneity, circumscribed tumors Williams et al. (1998), Kijima et al. (2014)  
Cell line xenograft Human GBM A172 xenograft High proliferation, used in various glioma studies, limited heterogeneity Finkelstein et al. (1994), Zhang et al. (2008)  
LN229 xenograft Human GBM LN229 xenograft High proliferation, MGMT methylation Hlavaty et al. (2011), Nagai et al. (2023)  
SF8628 xenograft Human GBM SF8628 xenograft H3.3K27M mutation, used in pediatric glioma studies Olow et al. (2016), Da-Veiga et al. (2023)  
IDH1 mutant xenograft Human GBM IDH1mut xenograft Retains IDH1 mutation, mimics genetic and phenotypic features of primary tumors. Challenging to maintain Luchman et al. (2012), Rudà et al. (2024)  
EGFRvIII xenograft Human GBM GLI36-EGFRvIII xenograft Overexpression of EGFRvIII, aggressive tumor growth Herrmann et al. (2016), Saydam et al. (2005)  
Xenograft Human GBM GSC xenograft CD133+ cells, tumor-initiating capability. Preserves tumor heterogeneity. Long latency periods Lee et al. (2006), Tanaka et al. (2019)  
Xenograft Human GBM PDX Retains some genetic and histological features of the primary tumor. Preserves tumor heterogeneity. Requires fresh tumor samples with variable success rates Kerstetter-Fogle et al. (2020), Vaubel et al. (2020)  
ModelOriginNameCharacteristicsCitations
Established cell lines Human GBM U87 High proliferation, non-diffuse, infiltrative patterns, widely used, well-characterized Clark et al. (2010), Allen et al. (2016)  
Established cell line Human GBM U251 High proliferation, necrotic regions, high Ki-67 positivity, maintains some tumor cell infiltrative patterns Torsvik et al. (2014), Li et al. (2017)  
Established cell line Human GBM T98G High ACTA2 expression, motility, minimally tumorigenic in mice Kiseleva et al. (2016), Rubenstein et al. (1999)  
Established cell line Human GBM A172 High proliferation Fenstermaker et al. (1998), Kiseleva et al. (2016)  
Established cell line Human GBM LN229 High proliferation, useful for studying MGMT methylation and drug response Beckner et al. (2005), Demircan et al. (2021)  
Established cell line Human GBM SF8628 H3.3K27M mutation, used in pediatric glioma studies Damanskienė et al. (2022), Olow et al. (2016)  
Established cell line Human GBM U373 High proliferation, widely used, well-characterized Dranoff et al. (1985), Takiguchi et al. (1985)  
Established cell line Human GBM SF9402 H3.3 wild type, used in combination therapy studies Hashizume et al. (2014), Wang et al. (2021)  
Established cell line Human GBM SF7761 H3.3K27M mutation, used in pediatric glioma studies Hashizume et al. (2012), Abe et al. (2020)  
Established cell line Human GBM GBM12 High proliferation, used in xenograft studies Sarkaria et al. (2006), Paraskevakou et al. (2007)  
Established cell line Human oligodendroglioma Hs683 High proliferation, useful for studying TMZ response Tasiou et al. (2001), Konduri et al. (2001)  
Established cell line Mouse GBM GL261 High MHC I, MHC II expression, RAS and p53 mutations. Widely used in immunotherapy studies Wu et al. (2008), Rappa et al. (2008)  
Established cell line Rat gliosarcoma 9L High proliferation, aggressive tumor growth in vivo Ghods et al. (2007), Kruse et al. (1994)  
Established cell line Rat GBM C6 High proliferation, aggressive tumor growth in vivo Giakoumettis et al. (2018), Kondo et al. (2004)  
3D models Human GBM GSCs Retains patient’s molecular subtypes Singh et al. (2004), Lee et al. (2006)  
3D models Human GBM PDOs Recapitulates inter- and intra-tumoral heterogeneity. Requires fresh tumor samples Chen et al. (2022), Jacob et al. (2020)  
3D models Human GBM GLICOs Allows for diffuse infiltration of glioma cells, mimicking human brain integration. Represents epigenomic-mediated transcriptomic states da Silva et al. (2018), Linkous et al. (2019)  
3D models Human GBM Cerebral organoids with CRISPR-Cas9 (GBM organoids) Genetically manipulated to develop oncogenic properties. Limited tumor heterogeneity Ogawa et al. (2018), Bian et al. (2018)  
3D models Human GBM Tumor organoids Represents hypoxic niches and oxygen gradients. Lack interactions with normal host brain cells Hubert et al. (2016), Heaster et al. (2019)  
3D models Human and rodent brain tissue Brain slice cultures (explants) Allows interaction with normal brain cells and ECM. Limited by the stress and eventual death of normal brain constituents Ohnishi et al. (1998), Eisemann et al. (2018)  
Oncogene induced syngeneic mouse models C57BL/6 mouse SB28 Poor immunogenic glioma model, commonly used in PD-L immunotherapy studies Letchuman et al. (2022), Murty et al. (2020)  
Chemically induced syngeneic mouse models C57BL/6 mouse GL261 High proliferation, aggressive tumor growth, mutation in KRAS. Genetic drift over time, limited representation of human gliomas, immunogenic. Szatmári et al. (2006), Daviaud et al. (2024)  
Chemically induced C57BL/6 mouse CT-2A Deficient in PTEN, necrotic, chemoresistant, undergoes unregulated angiogenesis. Used in immunotherapy studies limited genetic heterogeneity Riva et al. (2019), Casanova-Carvajal et al. (2019)  
Chemically induced C57BL/6 mouse GL26 High proliferation, mutation in KRAS, aggressive tumor growth, widely used Wouters et al. (2020), Kim et al. (2010)  
Spontaneous syngeneic models C3H mouse P560 High proliferation, aggressive tumor growth Kim et al. (2010), Bradford et al. (1986)  
GEMMs Neural progenitors or astrocytes Ink4a-Arf/Kras/Akt Model for studying cooperation between KRas activation and Ink4a-Arf loss in gliomagenesis Uhrbom et al. (2002), Figg et al. (2024)  
GEMMs Various glioma-initiating cells PTEN/p53/CDKN2/RB knockout Models high-grade astrocytomas with multiple genetic alterations Holland (2001), Alcantara Llaguno et al. (2019)  
GEMMs Neural stem/progenitor cells NF1/p53 Useful for studying NF1 and p53 interactions in gliomagenesis. Induces tumors that appear similar to astrocytomas Zhu et al. (2005), Liu et al. (2011)  
GEMMs Various glioma-initiating cells Idh1R132H Investigates metabolic vulnerabilities of IDH1 mutant gliomas. Demonstrates extreme vulnerability to NAD+ depletion Bardella et al. (2016), Zhang et al. (2019)  
GEMMs Various glioma-initiating cells CDKN2 Knockout/EGFR/PDGFR Studies cooperation between CDKN2 loss and growth factor signaling in gliomagenesis Zhu et al. (2009), Yeo et al. (2021)  
Xenograft models Human GBM U87MG xenograft High proliferation, circumscribed tumors. Widely used, good reproducibility. Lacks infiltrative pattern seen in human gliomas Mathieu et al. (2008), Donoghue et al. (2011)  
Cell line xenograft Human GBM U251 xenograft High proliferation, necrotic regions, well-characterized, widely used, limited heterogeneity, circumscribed tumors Williams et al. (1998), Kijima et al. (2014)  
Cell line xenograft Human GBM A172 xenograft High proliferation, used in various glioma studies, limited heterogeneity Finkelstein et al. (1994), Zhang et al. (2008)  
LN229 xenograft Human GBM LN229 xenograft High proliferation, MGMT methylation Hlavaty et al. (2011), Nagai et al. (2023)  
SF8628 xenograft Human GBM SF8628 xenograft H3.3K27M mutation, used in pediatric glioma studies Olow et al. (2016), Da-Veiga et al. (2023)  
IDH1 mutant xenograft Human GBM IDH1mut xenograft Retains IDH1 mutation, mimics genetic and phenotypic features of primary tumors. Challenging to maintain Luchman et al. (2012), Rudà et al. (2024)  
EGFRvIII xenograft Human GBM GLI36-EGFRvIII xenograft Overexpression of EGFRvIII, aggressive tumor growth Herrmann et al. (2016), Saydam et al. (2005)  
Xenograft Human GBM GSC xenograft CD133+ cells, tumor-initiating capability. Preserves tumor heterogeneity. Long latency periods Lee et al. (2006), Tanaka et al. (2019)  
Xenograft Human GBM PDX Retains some genetic and histological features of the primary tumor. Preserves tumor heterogeneity. Requires fresh tumor samples with variable success rates Kerstetter-Fogle et al. (2020), Vaubel et al. (2020)  

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