Integrating the Glioblastoma Microenvironment Into Engineered Experimental Models

Abstract

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed.

Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

“…These include hyaluronic acid 90,91 , chitosan 92 , chondroitin sulfate polysaccharides 93 , alginates 92 and collagen/gelatin proteins 90,94 . The use of these hydrogels in GBM has been extensively reviewed by Xiao 95 , so will not be discussed in this review any further. Matrigel is a natural hydrogel of animal origin that has been extensively used in the GBM field both as a coating-material or as a 3D growth system and will be discussed further in the sections below.…”

A human co‐culture cell model incorporating microglia supports glioblastoma growth and migration, and confers resistance to cytotoxics

“…2 GBM cells dynamically respond to their local microenvironment, thereby affecting tumor cell behavior. 5,6 Non-neoplastic cells associated with GBM are glial, immune, microglial, vascular endothelial, pericytic and neuronal in nature. 5,6 Non-neoplastic cells associated with GBM are glial, immune, microglial, vascular endothelial, pericytic and neuronal in nature.…”

Biomimetic Strategies for the Glioblastoma Microenvironment

“…Unlike two-dimensional (2D) models, in vitro 3D GBM models can replicate the highly complex microenvironment of in vivo GBM niches. Furthermore, well-defined 3D in vitro GBM niches are simpler and more reliable than in vivo animal models, which involve costly, time-consuming technical procedures (Xiao et al, 2017). Here, we presented an overview of the biomimetic approaches for reconstructing in vitro 3D GBM models of anatomical and matrix-related aspects of the GBM microenvironment (see also …”

“…During tumor progression, cancer cells remodel dynamically and interact reciprocally with their microenvironment (both the cellular and non-cellular components), leading to the formation of a tumor-favorable environment (Quail and Joyce, 2013). Many recent studies have highlighted the importance of targeting tumor microenvironment to reduce tumor malignancy (Cuddapah et al, 2014;Hambardzumyan and Bergers, 2015;Xiao et al, 2017). For further progress in the development of in vitro GBM models, the other components of brain tumor microenvironment should be considered to better understand glioblastoma invasion.…”