A novel neural stem cell-derived immunocompetent mouse model of glioblastoma for preclinical studies
Barbara Costa, Michael NC Fletcher, Pavle Boskovic, Ekaterina L Ivanova, Tanja Eisemann, Sabrina Lohr, Lukas Bunse, Martin Loewer, Stefanie Burchard, Andrey Korshunov, Hai-Kun Liu, Michael Platten, Bernhard Radlwimmer, Peter Angel, Heike Peterziel
Received Date: 2nd March 20
Glioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneic in vivo models 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 repeated in-vivo passaging 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.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.