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Preclinical Experimental Models for Human Glioma

  • Diya Zhang
  • Yunfan Li
  • Yucheng Wang
  • Rui Ju
  • Lei Guo


Gliomas are one of the most common incurable brain tumors in adults with poor prognosis. Attempts at modeling human gliomas over the past decades have not only improved our knowledge of glioma biology but also boosted the development of therapeutic strategies. Despite great endeavors, gliomas are not responsive to the current tumor treatments, such as radiotherapy, chemotherapy, and immunotherapy due to their high inter- and intra-heterogenic tumor microenvironment (TME) and immune suppressive landscape. Therefore, it is significant to utilize suitable models to investigate the tumorigenesis, progression, and invasion of gliomas and evaluate potential therapies. Ideally, glioma models should fully recapitulate the genetic alterations and histological characteristics of the parental tumor, as well as reproduce the interactions between the tumor and its TME. In this review, we will discuss and compare the pros and cons of the current glioma models including traditional mouse models, established cell lines, newly 3D-cultured organoids, and 3D bioprinting glioma models in glioma pathogenesis research and therapy evaluation.



  1. Abate, L. E., Mukherjee, P., & Seyfried, T. N. (2006). Gene-linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma. J Neurochem, 98(6), 1973-1984. doi:10.1111/j.1471-4159.2006.04097.x
  2. Ahmad, M., Frei, K., Willscher, E., Stefanski, A., Kaulich, K., Roth, P., . . . Weller, M. (2014). How stemlike are sphere cultures from long-term cancer cell lines? Lessons from mouse glioma models. J Neuropathol Exp Neurol, 73(11), 1062-1077. doi:10.1097/nen.0000000000000130
  3. Akbarnejad, Z., Eskandary, H., Dini, L., Vergallo, C., Nematollahi-Mahani, S. N., Farsinejad, A., . . . Ahmadi, M. (2017). Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G). Biomed Pharmacother, 92, 254-264. doi:10.1016/j.biopha.2017.05.050
  4. Allen, M., Bjerke, M., Edlund, H., Nelander, S., & Westermark, B. (2016). Origin of the U87MG glioma cell line: Good news and bad news. Sci Transl Med, 8(354), 354re353. doi:10.1126/scitranslmed.aaf6853
  5. Ausman, J. I., Shapiro, W. R., & Rall, D. P. (1970). Studies on the chemotherapy of experimental brain tumors: development of an experimental model. Cancer Res, 30(9), 2394-2400.
  6. Bejarano, L., Jordao, M. J. C., & Joyce, J. A. (2021). Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov, 11(4), 933-959. doi:10.1158/2159-8290.CD-20-1808
  7. Ben-David, U., Ha, G., Tseng, Y. Y., Greenwald, N. F., Oh, C., Shih, J., . . . Golub, T. R. (2017). Patient-derived xenografts undergo mouse-specific tumor evolution. Nat Genet, 49(11), 1567-1575. doi:10.1038/ng.3967
  8. Binello, E., Qadeer, Z. A., Kothari, H. P., Emdad, L., & Germano, I. M. (2012). Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro. J Cancer, 3, 166-174. doi:10.7150/jca.4149
  9. Boccellato, C., & Rehm, M. (2022). Glioblastoma, from disease understanding towards optimal cell-based in vitro models. Cell Oncol (Dordr), 45(4), 527-541. doi:10.1007/s13402-022-00684-7
  10. Bosenberg, M., Liu, E. T., Yu, C. I., & Palucka, K. (2023). Mouse models for immuno-oncology. Trends Cancer, 9(7), 578-590. doi:10.1016/j.trecan.2023.03.009
  11. Candolfi, M., Curtin, J. F., Nichols, W. S., Muhammad, A. G., King, G. D., Pluhar, G. E., . . . Castro, M. G. (2007). Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neurooncol, 85(2), 133-148. doi:10.1007/s11060-007-9400-9
  12. Chen, R., Smith-Cohn, M., Cohen, A. L., & Colman, H. (2017). Glioma Subclassifications and Their Clinical Significance. Neurotherapeutics, 14(2), 284-297. doi:10.1007/s13311-017-0519-x
  13. Chen, Z., & Hambardzumyan, D. (2018). Immune Microenvironment in Glioblastoma Subtypes. Front Immunol, 9, 1004. doi:10.3389/fimmu.2018.01004
  14. Chiu, M., Taurino, G., Bianchi, M. G., Ottaviani, L., Andreoli, R., Ciociola, T., . . . Bussolati, O. (2018). Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth. Int J Mol Sci, 19(4). doi:10.3390/ijms19041099
  15. Clevers, H. (2016). Modeling Development and Disease with Organoids. Cell, 165(7), 1586-1597. doi:10.1016/j.cell.2016.05.082
  16. Cohen, A. L., Holmen, S. L., & Colman, H. (2013). IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep, 13(5), 345. doi:10.1007/s11910-013-0345-4
  17. Dai, X., Ma, C., Lan, Q., & Xu, T. (2016). 3D bioprinted glioma stem cells for brain tumor model and applications of drug susceptibility. Biofabrication, 8(4), 045005. doi:10.1088/1758-5090/8/4/045005
  18. Daniel, V. C., Marchionni, L., Hierman, J. S., Rhodes, J. T., Devereux, W. L., Rudin, C. M., . . . Watkins, D. N. (2009). A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res, 69(8), 3364-3373. doi:10.1158/0008-5472.CAN-08-4210
  19. Fraser, H. (1971). Astrocytomas in an inbred mouse strain. J Pathol, 103(4), 266-270. doi:10.1002/path.1711030410
  20. Haddad, A. F., Young, J. S., Amara, D., Berger, M. S., Raleigh, D. R., Aghi, M. K., & Butowski, N. A. (2021). Mouse models of glioblastoma for the evaluation of novel therapeutic strategies. Neurooncol Adv, 3(1), vdab100. doi:10.1093/noajnl/vdab100
  21. Heinrich, M. A., Bansal, R., Lammers, T., Zhang, Y. S., Michel Schiffelers, R., & Prakash, J. (2019). 3D-Bioprinted Mini-Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics. Adv Mater, 31(14), e1806590. doi:10.1002/adma.201806590
  22. Heinrich, M. A., Liu, W., Jimenez, A., Yang, J., Akpek, A., Liu, X., . . . Zhang, Y. S. (2019). 3D Bioprinting: from Benches to Translational Applications. Small, 15(23), e1805510. doi:10.1002/smll.201805510
  23. Hermida, M. A., Kumar, J. D., Schwarz, D., Laverty, K. G., Di Bartolo, A., Ardron, M., . . . Leslie, N. R. (2020). Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models. Adv Biol Regul, 75, 100658. doi:10.1016/j.jbior.2019.100658
  24. Hetze, S., Sure, U., Schedlowski, M., Hadamitzky, M., & Barthel, L. (2021). Rodent Models to Analyze the Glioma Microenvironment. ASN Neuro, 13, 17590914211005074. doi:10.1177/17590914211005074
  25. Hicks, W. H., Bird, C. E., Traylor, J. I., Shi, D. D., El Ahmadieh, T. Y., Richardson, T. E., . . . Abdullah, K. G. (2021). Contemporary Mouse Models in Glioma Research. Cells, 10(3). doi:10.3390/cells10030712
  26. Huang, G. D., Chen, F. F., Ma, G. X., Li, W. P., Zheng, Y. Y., Meng, X. B., . . . Chen, L. (2021). Cassane diterpenoid derivative induces apoptosis in IDH1 mutant glioma cells through the inhibition of glutaminase in vitro and in vivo. Phytomedicine, 82, 153434. doi:10.1016/j.phymed.2020.153434
  27. Hubert, C. G., Rivera, M., Spangler, L. C., Wu, Q., Mack, S. C., Prager, B. C., . . . Rich, J. N. (2016). A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo. Cancer Res, 76(8), 2465-2477. doi:10.1158/0008-5472.CAN-15-2402
  28. Huszthy, P. C., Daphu, I., Niclou, S. P., Stieber, D., Nigro, J. M., Sakariassen, P. O., . . . Bjerkvig, R. (2012). In vivo models of primary brain tumors: pitfalls and perspectives. Neuro Oncol, 14(8), 979-993. doi:10.1093/neuonc/nos135
  29. Ishii, N., Maier, D., Merlo, A., Tada, M., Sawamura, Y., Diserens, A. C., & Van Meir, E. G. (1999). Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol, 9(3), 469-479. doi:10.1111/j.1750-3639.1999.tb00536.x
  30. Jacob, F., Ming, G. L., & Song, H. (2020). Generation and biobanking of patient-derived glioblastoma organoids and their application in CAR T cell testing. Nat Protoc, 15(12), 4000-4033. doi:10.1038/s41596-020-0402-9
  31. Jacob, F., Salinas, R. D., Zhang, D. Y., Nguyen, P. T. T., Schnoll, J. G., Wong, S. Z. H., . . . Song, H. (2020). A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. Cell, 180(1), 188-204 e122. doi:10.1016/j.cell.2019.11.036
  32. Jacobs, V. L., Valdes, P. A., Hickey, W. F., & De Leo, J. A. (2011). Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model. ASN Neuro, 3(3), e00063. doi:10.1042/AN20110014
  33. Jin, F., Jin-Lee, H. J., & Johnson, A. J. (2021). Mouse Models of Experimental Glioblastoma. In W. Debinski (Ed.), Gliomas. Brisbane (AU): Exon Publications. doi:10.36255/exonpublications.gliomas.2021.chapter2
  34. Johanns, T. M., Ward, J. P., Miller, C. A., Wilson, C., Kobayashi, D. K., Bender, D., . . . Dunn, G. P. (2016). Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach. Cancer Immunol Res, 4(12), 1007-1015. doi:10.1158/2326-6066.CIR-16-0156
  35. Jung, J., Seol, H. S., & Chang, S. (2018). The Generation and Application of Patient-Derived Xenograft Model for Cancer Research. Cancer Res Treat, 50(1), 1-10. doi:10.4143/crt.2017.307
  36. Kersten, K., de Visser, K. E., van Miltenburg, M. H., & Jonkers, J. (2017). Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med, 9(2), 137-153. doi:10.15252/emmm.201606857
  37. Khalsa, J. K., Cheng, N., Keegan, J., Chaudry, A., Driver, J., Bi, W. L., . . . Shah, K. (2020). Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types. Nat Commun, 11(1), 3912. doi:10.1038/s41467-020-17704-5
  38. Kijima, N., & Kanemura, Y. (2017). Mouse Models of Glioblastoma. In S. De Vleeschouwer (Ed.), Glioblastoma. Brisbane (AU): Codon Publications. doi:10.15586/codon.glioblastoma.2017.ch7
  39. Klein, E., Hau, A. C., Oudin, A., Golebiewska, A., & Niclou, S. P. (2020). Glioblastoma Organoids: Pre-Clinical Applications and Challenges in the Context of Immunotherapy. Front Oncol, 10, 604121. doi:10.3389/fonc.2020.604121
  40. Lenting, K., Verhaak, R., Ter Laan, M., Wesseling, P., & Leenders, W. (2017). Glioma: experimental models and reality. Acta Neuropathol, 133(2), 263-282. doi:10.1007/s00401-017-1671-4
  41. Letchuman, V., Ampie, L., Shah, A. H., Brown, D. A., Heiss, J. D., & Chittiboina, P. (2022). Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes. Neurosurg Focus, 52(2), E5. doi:10.3171/2021.11.FOCUS21556
  42. Linkous, A., Balamatsias, D., Snuderl, M., Edwards, L., Miyaguchi, K., Milner, T., . . . Fine, H. A. (2019). Modeling Patient-Derived Glioblastoma with Cerebral Organoids. Cell Rep, 26(12), 3203-3211 e3205. doi:10.1016/j.celrep.2019.02.063
  43. Liu, C. J., Schaettler, M., Blaha, D. T., Bowman-Kirigin, J. A., Kobayashi, D. K., Livingstone, A. J., . . . Dunn, G. P. (2020). Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine. Neuro Oncol, 22(9), 1276-1288. doi:10.1093/neuonc/noaa050
  44. Liu, Y., Wu, W., Cai, C., Zhang, H., Shen, H., & Han, Y. (2023). Patient-derived xenograft models in cancer therapy: technologies and applications. Signal Transduct Target Ther, 8(1), 160. doi:10.1038/s41392-023-01419-2
  45. Long, P. M., Tighe, S. W., Driscoll, H. E., Moffett, J. R., Namboodiri, A. M., Viapiano, M. S., . . . Jaworski, D. M. (2013). Acetate supplementation induces growth arrest of NG2/PDGFRalpha-positive oligodendroglioma-derived tumor-initiating cells. PLoS One, 8(11), e80714. doi:10.1371/journal.pone.0080714
  46. Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., . . . Ellison, D. W. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol, 23(8), 1231-1251. doi:10.1093/neuonc/noab106
  47. Ma, Q., Long, W., Xing, C., Chu, J., Luo, M., Wang, H. Y., . . . Wang, R. F. (2018). Cancer Stem Cells and Immunosuppressive Microenvironment in Glioma. Front Immunol, 9, 2924. doi:10.3389/fimmu.2018.02924
  48. Markwell, S. M., Ross, J. L., Olson, C. L., & Brat, D. J. (2022). Necrotic reshaping of the glioma microenvironment drives disease progression. Acta Neuropathol, 143(3), 291-310. doi:10.1007/s00401-021-02401-4
  49. Marsh, J., Mukherjee, P., & Seyfried, T. N. (2008). Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue/tuberous sclerosis complex 2-deficient mouse astrocytoma. Clin Cancer Res, 14(23), 7751-7762. doi:10.1158/1078-0432.CCR-08-0213
  50. Martínez-Murillo, R., & Martínez, A. (2007). Standardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells. Histol Histopathol, 22(12), 1309-1326. doi:10.14670/hh-22.1309
  51. Marumoto, T., Tashiro, A., Friedmann-Morvinski, D., Scadeng, M., Soda, Y., Gage, F. H., & Verma, I. M. (2009). Development of a novel mouse glioma model using lentiviral vectors. Nat Med, 15(1), 110-116. doi:10.1038/nm.1863
  52. Matai, I., Kaur, G., Seyedsalehi, A., McClinton, A., & Laurencin, C. T. (2020). Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials, 226, 119536. doi:10.1016/j.biomaterials.2019.119536
  53. McNeill, R. S., Vitucci, M., Wu, J., & Miller, C. R. (2015). Contemporary murine models in preclinical astrocytoma drug development. Neuro Oncol, 17(1), 12-28. doi:10.1093/neuonc/nou288
  54. Kleihues, P. (2010). Erwin G. Van Meir (ed): CNS cancer: Models, markers, prognostic factors, targets, and therapeutic approaches. J Neurooncol, 98(3), 435-436. doi:10.1007/s11060-009-0088-x
  55. Mukherjee, P., Abate, L. E., & Seyfried, T. N. (2004). Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors. Clin Cancer Res, 10(16), 5622-5629. doi:10.1158/1078-0432.Ccr-04-0308
  56. Murphy, S. V., De Coppi, P., & Atala, A. (2020). Opportunities and challenges of translational 3D bioprinting. Nat Biomed Eng, 4(4), 370-380. doi:10.1038/s41551-019-0471-7
  57. Neufeld, L., Yeini, E., Reisman, N., Shtilerman, Y., Ben-Shushan, D., Pozzi, S., . . . Satchi-Fainaro, R. (2021). Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment. Sci Adv, 7(34). doi:10.1126/sciadv.abi9119
  58. Nistér, M., & Westermark, B. (1994). 2 - Human Glioma Cell Lines. In R. J. Hay, J.-G. Park, & A. Gazdar (Eds.), Atlas of Human Tumor Cell Lines (pp. 17-42). San Diego: Academic Press.doi: 10.1016/B978-0-12-333530-2.50005-8
  59. Noorani, I. (2019). Genetically Engineered Mouse Models of Gliomas: Technological Developments for Translational Discoveries. Cancers (Basel), 11(9). doi:10.3390/cancers11091335
  60. Ogawa, J., Pao, G. M., Shokhirev, M. N., & Verma, I. M. (2018). Glioblastoma Model Using Human Cerebral Organoids. Cell Rep, 23(4), 1220-1229. doi:10.1016/j.celrep.2018.03.105
  61. Oh, T., Fakurnejad, S., Sayegh, E. T., Clark, A. J., Ivan, M. E., Sun, M. Z., . . . Parsa, A. T. (2014). Immunocompetent murine models for the study of glioblastoma immunotherapy. J Transl Med, 12, 107. doi:10.1186/1479-5876-12-107
  62. Okada, S., Vaeteewoottacharn, K., & Kariya, R. (2019). Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models. Cells, 8(8). doi:10.3390/cells8080889
  63. Ostrom, Q. T., Cioffi, G., Waite, K., Kruchko, C., & Barnholtz-Sloan, J. S. (2021). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol, 23(12 Suppl 2), iii1-iii105. doi:10.1093/neuonc/noab200
  64. Parra-Cantu, C., Li, W., Quiñones-Hinojosa, A., & Zhang, Y. S. (2020). 3D bioprinting of glioblastoma models. J 3D Print Med, 4(2), 113-125. doi:10.2217/3dp-2019-0027
  65. Parsons, D. W., Jones, S., Zhang, X., Lin, J. C., Leary, R. J., Angenendt, P., . . . Kinzler, K. W. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321(5897), 1807-1812. doi:10.1126/science.1164382
  66. Patil, V., Pal, J., & Somasundaram, K. (2015). Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing. Oncotarget, 6(41), 43452-43471. doi:10.18632/oncotarget.6171
  67. Pellegatta, S., Valletta, L., Corbetta, C., Patane, M., Zucca, I., Riccardi Sirtori, F., . . . Finocchiaro, G. (2015). Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun, 3, 4. doi:10.1186/s40478-014-0180-0
  68. Philip, B., Yu, D. X., Silvis, M. R., Shin, C. H., Robinson, J. P., Robinson, G. L., . . . Holmen, S. L. (2018). Mutant IDH1 Promotes Glioma Formation In Vivo. Cell Rep, 23(5), 1553-1564. doi:10.1016/j.celrep.2018.03.133
  69. Pilkington, G. J., Darling, J. L., Lantos, P. L., & Thomas, D. G. (1983). Cell lines (VMDk) derived from a spontaneous murine astrocytoma. Morphological and immunocytochemical characterization. J Neurol Sci, 62(1-3), 115-139. doi:10.1016/0022-510x(83)90193-4
  70. Ponten, J. (1975). Neoplastic human glia cells in culture. In J. Fogh (Ed.), Human Tumor Cells in Vitro (pp. 175-206). Boston, MA: Springer US. doi: 10.1007/978-1-4757-1647-4_7
  71. Ponten, J., & Macintyre, E. H. (1968). Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand, 74(4), 465-486. doi:10.1111/j.1699-0463.1968.tb03502.x
  72. Post, G. R., & Dawson, G. (1992). Characterization of a cell line derived from a human oligodendroglioma. Mol Chem Neuropathol, 16(3), 303-317. doi:10.1007/BF03159976
  73. Qiang, L., Yang, Y., Ma, Y. J., Chen, F. H., Zhang, L. B., Liu, W., . . . Guo, Q. L. (2009). Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett, 279(1), 13-21. doi:10.1016/j.canlet.2009.01.016
  74. Radaelli, E., Ceruti, R., Patton, V., Russo, M., Degrassi, A., Croci, V., . . . Alzani, R. (2009). Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease. Histol Histopathol, 24(7), 879-891. doi:10.14670/hh-24.879
  75. Rajan, R. G., Fernandez-Vega, V., Sperry, J., Nakashima, J., Do, L. H., Andrews, W., . . . Spicer, T. P. (2023). In Vitro and In Vivo Drug-Response Profiling Using Patient-Derived High-Grade Glioma. Cancers (Basel), 15(13). doi:10.3390/cancers15133289
  76. Rankin, S. L., Zhu, G., & Baker, S. J. (2012). Review: insights gained from modelling high-grade glioma in the mouse. Neuropathol Appl Neurobiol, 38(3), 254-270. doi:10.1111/j.1365-2990.2011.01231.x
  77. Ratliff, M., Kim, H., Qi, H., Kim, M., Ku, B., Azorin, D. D., . . . Kwon, Y.-J. (2022). Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma. International Journal of Molecular Sciences, 23(12). doi:10.3390/ijms23126572
  78. Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., . . . Yan, H. (2011). Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci U S A, 108(8), 3270-3275. doi:10.1073/pnas.1019393108
  79. Ren, A. L., Wu, J. Y., Lee, S. Y., & Lim, M. (2023). Translational Models in Glioma Immunotherapy Research. Curr Oncol, 30(6), 5704-5718. doi:10.3390/curroncol30060428
  80. Riva, M., Wouters, R., Sterpin, E., Giovannoni, R., Boon, L., Himmelreich, U., . . . Coosemans, A. (2021). Radiotherapy, Temozolomide, and Antiprogrammed Cell Death Protein 1 Treatments Modulate the Immune Microenvironment in Experimental High-Grade Glioma. Neurosurgery, 88(2), E205-e215. doi:10.1093/neuros/nyaa421
  81. Ruiz-Garcia, H., Alvarado-Estrada, K., Schiapparelli, P., Quinones-Hinojosa, A., & Trifiletti, D. M. (2020). Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment. Front Cell Neurosci, 14, 558381. doi:10.3389/fncel.2020.558381
  82. Ryu, C. H., Yoon, W. S., Park, K. Y., Kim, S. M., Lim, J. Y., Woo, J. S., . . . Jeun, S. S. (2012). Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. J Biomed Biotechnol, 2012, 987495. doi:10.1155/2012/987495
  83. Sampson, J. H., Ashley, D. M., Archer, G. E., Fuchs, H. E., Dranoff, G., Hale, L. P., & Bigner, D. D. (1997). Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion. Neurosurgery, 41(6), 1365-1372; discussion 1372-1363. doi:10.1097/00006123-199712000-00024
  84. Schulz, J. A., Rodgers, L. T., Kryscio, R. J., Hartz, A. M. S., & Bauer, B. (2022). Characterization and comparison of human glioblastoma models. BMC Cancer, 22(1), 844. doi:10.1186/s12885-022-09910-9
  85. Seligman, A. M., Shear, M. J., & Alexander, L. (1939). Studies in carcinogenesis: VIII. Experimental production of brain tumors in mice with methylcholanthrene. Am J Cancer Res, 37(3), 364-395. doi: 10.1158/ajc.1939.364
  86. Serano, R. D., Pegram, C. N., & Bigner, D. D. (1980). Tumorigenic cell culture lines from a spontaneous VM/Dk murine astrocytoma (SMA). Acta Neuropathol, 51(1), 53-64. doi:10.1007/bf00688850
  87. Seyfried, T. N., el-Abbadi, M., & Roy, M. L. (1992). Ganglioside distribution in murine neural tumors. Mol Chem Neuropathol, 17(2), 147-167. doi:10.1007/BF03159989
  88. Seyfried, T. N., & Mukherjee, P. (2010). Ganglioside GM3 Is Antiangiogenic in Malignant Brain Cancer. J Oncol, 2010, 961243. doi:10.1155/2010/961243
  89. Shelton, L. M., Mukherjee, P., Huysentruyt, L. C., Urits, I., Rosenberg, J. A., & Seyfried, T. N. (2010). A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion. J Neurooncol, 99(2), 165-176. doi:10.1007/s11060-010-0115-y
  90. Shi, J., Dong, X., Han, W., Zhou, P., Liu, L., Wang, H., . . . Dong, J. (2022). Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma. Anticancer Drugs, 33(1), e381-e388. doi:10.1097/CAD.0000000000001217
  91. Shukla, P., Yeleswarapu, S., Heinrich, M. A., Prakash, J., & Pati, F. (2022). Mimicking tumor microenvironment by 3D bioprinting: 3D cancer modeling. Biofabrication, 14(3). doi:10.1088/1758-5090/ac6d11
  92. Silginer, M., Papa, E., Szabó, E., Vasella, F., Pruschy, M., Stroh, C., . . . Weller, M. (2023). Immunological and tumor-intrinsic mechanisms mediate the synergistic growth suppression of experimental glioblastoma by radiotherapy and MET inhibition. Acta Neuropathol Commun, 11(1), 41. doi:10.1186/s40478-023-01527-8
  93. Stringer, B. W., Day, B. W., D'Souza, R. C. J., Jamieson, P. R., Ensbey, K. S., Bruce, Z. C., . . . Boyd, A. W. (2019). A reference collection of patient-derived cell line and xenograft models of proneural, classical and mesenchymal glioblastoma. Sci Rep, 9(1), 4902. doi:10.1038/s41598-019-41277-z
  94. Stylli, S. S., Luwor, R. B., Ware, T. M., Tan, F., & Kaye, A. H. (2015). Mouse models of glioma. J Clin Neurosci, 22(4), 619-626. doi:10.1016/j.jocn.2014.10.013
  95. Suva, M. L., & Tirosh, I. (2020). The Glioma Stem Cell Model in the Era of Single-Cell Genomics. Cancer Cell, 37(5), 630-636. doi:10.1016/j.ccell.2020.04.001
  96. Szatmari, T., Lumniczky, K., Desaknai, S., Trajcevski, S., Hidvegi, E. J., Hamada, H., & Safrany, G. (2006). Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci, 97(6), 546-553. doi:10.1111/j.1349-7006.2006.00208.x
  97. Tang, L. W., Mallela, A. N., Deng, H., Richardson, T. E., Hervey-Jumper, S. L., McBrayer, S. K., & Abdullah, K. G. (2023). Preclinical modeling of lower-grade gliomas. Front Oncol, 13, 1139383. doi:10.3389/fonc.2023.1139383
  98. Tang, M., Rich, J. N., & Chen, S. (2021). Biomaterials and 3D Bioprinting Strategies to Model Glioblastoma and the Blood-Brain Barrier. Adv Mater, 33(5), e2004776. doi:10.1002/adma.202004776
  99. Tang, M., Xie, Q., Gimple, R. C., Zhong, Z., Tam, T., Tian, J., . . . Rich, J. N. (2020). Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions. Cell Res, 30(10), 833-853. doi:10.1038/s41422-020-0338-1
  100. Torsvik, A., Stieber, D., Enger, P. O., Golebiewska, A., Molven, A., Svendsen, A., . . . Bjerkvig, R. (2014). U-251 revisited: genetic drift and phenotypic consequences of long-term cultures of glioblastoma cells. Cancer Med, 3(4), 812-824. doi:10.1002/cam4.219
  101. Van Meir, E. G., Hadjipanayis, C. G., Norden, A. D., Shu, H. K., Wen, P. Y., & Olson, J. J. (2010). Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin, 60(3), 166-193. doi:10.3322/caac.20069
  102. Vaubel, R. A., Tian, S., Remonde, D., Schroeder, M. A., Mladek, A. C., Kitange, G. J., . . . Sarkaria, J. N. (2020). Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma. Clin Cancer Res, 26(5), 1094-1104. doi:10.1158/1078-0432.CCR-19-0909
  103. Verhaak, R. G., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., . . . Cancer Genome Atlas Research, N. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 17(1), 98-110. doi:10.1016/j.ccr.2009.12.020
  104. Wachsberger, P. R., Burd, R., Cardi, C., Thakur, M., Daskalakis, C., Holash, J., . . . Dicker, A. P. (2007). VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma. Int J Radiat Oncol Biol Phys, 67(5), 1526-1537. doi:10.1016/j.ijrobp.2006.11.011
  105. Wang, H., Cai, S., Bailey, B. J., Reza Saadatzadeh, M., Ding, J., Tonsing-Carter, E., . . . Pollok, K. E. (2017). Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an MDM2 antagonist. J Neurosurg, 126(2), 446-459. doi:10.3171/2016.1.JNS152513
  106. Wang, X., Dai, X., Zhang, X., Ma, C., Li, X., Xu, T., & Lan, Q. (2019). 3D bioprinted glioma cell-laden scaffolds enriching glioma stem cells via epithelial-mesenchymal transition. J Biomed Mater Res A, 107(2), 383-391. doi:10.1002/jbm.a.36549
  107. Wang, X., Li, X., Dai, X., Zhang, X., Zhang, J., Xu, T., & Lan, Q. (2018). Bioprinting of glioma stem cells improves their endotheliogenic potential. Colloids Surf B Biointerfaces, 171, 629-637. doi:10.1016/j.colsurfb.2018.08.006
  108. Wang, X., Li, X., Ding, J., Long, X., Zhang, H., Zhang, X., . . . Xu, T. (2021). 3D bioprinted glioma microenvironment for glioma vascularization. J Biomed Mater Res A, 109(6), 915-925. doi:10.1002/jbm.a.37082
  109. Wang, X. W., Labussiere, M., Valable, S., Peres, E. A., Guillamo, J. S., Bernaudin, M., & Sanson, M. (2014). IDH1(R132H) mutation increases U87 glioma cell sensitivity to radiation therapy in hypoxia. Biomed Res Int, 2014, 198697. doi:10.1155/2014/198697
  110. Wei, J., Chen, P., Gupta, P., Ott, M., Zamler, D., Kassab, C., . . . Heimberger, A. B. (2020). Immune biology of glioma-associated macrophages and microglia: functional and therapeutic implications. Neuro Oncol, 22(2), 180-194. doi:10.1093/neuonc/noz212
  111. Weller, M., Wick, W., Aldape, K., Brada, M., Berger, M., Pfister, S. M., . . . Reifenberger, G. (2015). Glioma. Nat Rev Dis Primers, 1, 15017. doi:10.1038/nrdp.2015.17
  112. Wu, A., Oh, S., Wiesner, S. M., Ericson, K., Chen, L., Hall, W. A., . . . Ohlfest, J. R. (2008). Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties. Stem Cells Dev, 17(1), 173-184. doi:10.1089/scd.2007.0133
  113. Wu, B. X., Wu, Z., Hou, Y. Y., Fang, Z. X., Deng, Y., Wu, H. T., & Liu, J. (2023). Application of three-dimensional (3D) bioprinting in anti-cancer therapy. Heliyon, 9(10), e20475. doi:10.1016/j.heliyon.2023.e20475
  114. Xu, C., Yuan, X., Hou, P., Li, Z., Wang, C., Fang, C., & Tan, Y. (2023). Development of glioblastoma organoids and their applications in personalized therapy. Cancer Biol Med, 20(5), 353-368. doi:10.20892/j.issn.2095-3941.2023.0061
  115. Xu, X., Li, L., Luo, L., Shu, L., Si, X., Chen, Z., . . . Ke, Y. (2021). Opportunities and challenges of glioma organoids. Cell Commun Signal, 19(1), 102. doi:10.1186/s12964-021-00777-0
  116. Yi, H. G., Jeong, Y. H., Kim, Y., Choi, Y. J., Moon, H. E., Park, S. H., . . . Cho, D. W. (2019). A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng, 3(7), 509-519. doi:10.1038/s41551-019-0363-x
  117. Yoshida, G. J. (2020). Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol, 13(1), 4. doi:10.1186/s13045-019-0829-z
  118. Yu, S. C., Ping, Y. F., Yi, L., Zhou, Z. H., Chen, J. H., Yao, X. H., . . . Bian, X. W. (2008). Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87. Cancer Lett, 265(1), 124-134. doi:10.1016/j.canlet.2008.02.010
  119. Zagzag, D., Amirnovin, R., Greco, M. A., Yee, H., Holash, J., Wiegand, S. J., . . . Grumet, M. (2000). Vascular apoptosis and involution in gliomas precede neovascularization: a novel concept for glioma growth and angiogenesis. Lab Invest, 80(6), 837-849. doi:10.1038/labinvest.3780088
  120. Zalles, M., & Towner, R. A. (2021). Pre-Clinical Models and Potential Novel Therapies for Glioblastomas. In W. Debinski (Ed.), Gliomas. Brisbane (AU): Exon Publications. doi:10.36255/exonpublications.gliomas.2021.chapter1
  121. Zhang, C., Jin, M., Zhao, J., Chen, J., & Jin, W. (2020). Organoid models of glioblastoma: advances, applications and challenges. Am J Cancer Res, 10(8), 2242-2257.
  122. Zimmerman, H. M., & Arnold, H. (1941). Experimental Brain Tumors. I. Tumors Produced with Methylcholanthrene. Cancer Res, 1(12), 919–938.

How to Cite

Zhang, Diya, et al. “Preclinical Experimental Models for Human Glioma”. Human Brain, vol. 2, no. 4, Dec. 2023, doi:10.37819/hb.4.1789.





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Published: 2023-12-30

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