Abstract
Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease.
Highlights
Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system (CNS) [1]
A refinement of the in vitro techniques was required to produce humanized GBM models based on the threedimensional (3D) culture of GBM cells in a system that reproduced the microenvironment of human brain tumors (Figure 2)
As time has passed since the first discoveries and advances in the study of GBM using cultures of cells, and mouse models new techniques are defining the future of GBM studies, which will probably be characterized by the use of individual organoids combined with single cell sequencing of genetic alterations to understand the processes involved in GBM origin and development
Summary
Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system (CNS) [1]. In vivo transplants of GBM in animal models have long been used to study tumor development upon the engraftment of human cells into immunodeficient mice.
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