Biomimetic Strategies for the Glioblastoma Microenvironment

Abstract

Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

Graphene-Induced Transdifferentiation of Cancer Stem Cells as a Therapeutic Strategy against Glioblastoma

“…The highly vascularized niche at the core of GBM represents an extremely favorable environment for CSCs by promoting their survival, hence maintaining GBM heterogeneity and aggressiveness [31][32][33] . A precise tuning of the surrounding microenvironment thus appears critical to the GBM SCs phenotype 34 .…”

“…A common approach for tissue engineering application is to develop 3D foams 55 . The main discernment that needs to be made between 2D and 3D models is that the former, although useful for traditional imaging methods, present a few challenges in mimicking the necessary structure, while the latter have been shown to be extremely well adapted for the in vitro culture of CSCs 34,57 .…”

Progress in mimicking brain microenvironments to understand and treat neurological disorders

“… 6–8 Yet, growing knowledge of the role of the brain microenvironment in homeostasis and regeneration has inspired tissue engineering strategies to bolster outcomes in disorders such as traumatic brain injury, stroke, and multiple sclerosis. 9–11 These design principles have been further applied to generate models for cancer and neurodegenerative diseases, 12,13 and mechanistic insights from these platforms will eventually lead to strategies to slow and potentially cure these disorders.…”

A versatile cancer cell trapping and 1D migration assay in a microfluidic device

“…Numerous 3D matrix scaffold-based models have also been developed specifically for GBM, typically in an attempt to mimic the abundant glycoproteins and proteoglycans like hyaluronic acid in the brain ECM, as opposed to the stiffer collagen ECM matrix typically found in other organs. [25][26][27][28] Given the strong influence that the tumor microenvironment topography can have on the behavior of single cells, many biomimetic platforms specifically emphasizing the fibrous nature of the ECM have also been developed using microfabrication techniques. 29 In an attempt to mimic the topographical guidance of single cancer cells, researchers have used aligned or randomly oriented electrospun nanofibers to mimic different tumor ECM microenvironments.…”