Practical Review on Preclinical Human 3D Glioblastoma Models: Advances and Challenges for Clinical Translation

Abstract

Fifteen years after the establishment of the Stupp protocol as the standard of care to treat glioblastomas, no major clinical advances have been achieved and increasing patient’s overall survival remains a challenge. Nevertheless, crucial molecular and cellular findings revealed the intra-tumoral and inter-tumoral complexities of these incurable brain tumors, and the essential role played by cells of the microenvironment in the lack of treatment efficacy. Taking this knowledge into account, fulfilling gaps between preclinical models and clinical samples is necessary to improve the successful rate of clinical trials. Since the beginning of the characterization of brain tumors initiated by Bailey and Cushing in the 1920s, several glioblastoma models have been developed and improved. In this review, we focused on the most widely used 3D human glioblastoma models, including spheroids, tumorospheres, organotypic slices, explants, tumoroids and glioblastoma-derived from cerebral organoids. We discuss their history, development and especially their usefulness.

Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

“…Recently, different 3D bio-mimicking human glioblastoma cell culture models have been advanced to more faithfully reconstitute glioblastoma complexity and better mimic its response to therapy [8]. Spheroids are widely used glioblastoma 3D models, which enable high-throughput testing of various therapeutic options with higher reproducibility at an affordable price [9]. Next to the spheroid, various scaffold-based 3D glioblastoma models were developed with the intention to mimic interactions between cancer cells and the extracellular matrix (ECM) [9,10].…”

“…Spheroids are widely used glioblastoma 3D models, which enable high-throughput testing of various therapeutic options with higher reproducibility at an affordable price [9]. Next to the spheroid, various scaffold-based 3D glioblastoma models were developed with the intention to mimic interactions between cancer cells and the extracellular matrix (ECM) [9,10]. Among them, alginate is one of the most commonly used polymers for microencapsulation and the development of scaffold-based 3D cell cultures.…”

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

“…In vitro, glioblastoma cells can also be cultivated as 3D spheroids or organoids [ 165 , 166 , 167 , 178 ]. As in 2D cultures, the tumor-surrounding microenvironment is absent.…”

Patient-Derived Organoids as a Model for Cancer Drug Discovery

“…However, it may be useful in the future to develop media containing the relevant supplements and growth factors, as this has previously been demonstrated to improve the metabolic fidelity and biological relevance for in vitro models [ 22 ]. Organoids which maintain the morphological and histological features of the original tumour have been developed to establish and culture PDOs from many common tumour types, including glioblastoma [ 23 ], breast [ 24 ], pancreas [ 25 ], prostate [ 26 , 27 ], liver [ 28 ], lung [ 4 , 29 ] and colon [ 30 ], with varying degrees of success and reproducibility.…”