6533b7dcfe1ef96bd1272afe
RESEARCH PRODUCT
A novel neural stem cell-derived immunocompetent mouse model of glioblastoma for preclinical studies
Lukas BunseEkaterina L IvanovaHai-kun LiuSabrina LohrMichael Nc FletcherAndrey KorshunovMichael PlattenTanja EisemannPeter AngelMartin LoewerPavle BoskovicStefanie BurchardBernhard RadlwimmerHeike PeterzielBarbara Costasubject
MyeloidCellBrain tumorBiologymedicine.diseaseNeural stem cellnervous system diseasesTranscriptomemedicine.anatomical_structureCell cultureGliomamedicineCancer researchbiology.proteinPTENneoplasmsdescription
AbstractGlioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneicin vivomodels that closely mirror human glioblastoma, including interactions between tumor and immune cells, are urgently needed for deciphering glioma biology and developing more effective treatments. Here, we generated glioblastoma cell lines by repeatedin-vivopassaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts they formed high-grade gliomas that faithfully recapitulated the histopathological features, invasiveness and myeloid cell infiltration characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioblastoma pathomechanism and test novel treatments, especially immunotherapies in syngeneic preclinical models.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-16 |