Understanding current experimental models of glioblastoma-brain microenvironment interactions

Abstract

Glioblastoma (GBM) is a common and devastating primary brain tumor, with median survival of 16-18 months after diagnosis in the setting of substantial resistance to standard-of-care and inevitable tumor recurrence. Recent work has implicated the brain microenvironment as being critical for GBM proliferation, invasion, and resistance to treatment. GBM does not operate in isolation, with neurons, astrocytes, and multiple immune populations being implicated in GBM tumor progression and invasiveness. The goal of this review article is to provide an overview of the available in vitro, ex vivo, and in vivo experimental models for assessing GBM-brain interactions, as well as discuss each model's relative strengths and limitations. Current in vitro models discussed will include 2D and 3D co-culture platforms with various cells of the brain microenvironment, as well as spheroids, whole organoids, and models of fluid dynamics, such as interstitial flow. An overview of in vitro and ex vivo organotypic GBM brain slices is also provided. Finally, we conclude with a discussion of the various in vivo rodent models of GBM, including xenografts, syngeneic grafts, and genetically-engineered models of GBM.

Keywords: GBM models; Glioblastoma; Tumor microenvironment.

Fig. 1

Graphical summary of in vitro GBM models (2D and 3D co-cultures, spheroids, organoids), ex vivo GBM brain slices, and in vivo GBM mouse models. These experimental models can recapitulate GBM interactions with cells of the brain microenvironment (neurons, oligodendrocytes, astrocytes, microglia, macrophages, and other immune cells) to varying extents as outlined in the text. This figure was created with BioRender (https://www.biorender.com)