Advanced Spheroid, Tumouroid and 3D Bioprinted In-Vitro Models of Adult and Paediatric Glioblastoma.

Louise Orcheston-Findlay,Geraldine O’Neill,Samuel Bax,Robert Utama,Dinisha Govender,Martin Engel

doi:10.3390/ijms22062962

Louise Orcheston-Findlay, Geraldine O’Neill + Show 4 more

Open Access

https://doi.org/10.3390/ijms22062962

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Abstract

The life expectancy of patients with high-grade glioma (HGG) has not improved in decades. One of the crucial tools to enable future improvement is advanced models that faithfully recapitulate the tumour microenvironment; they can be used for high-throughput screening that in future may enable accurate personalised drug screens. Currently, advanced models are crucial for identifying and understanding potential new targets, assessing new chemotherapeutic compounds or other treatment modalities. Recently, various methodologies have come into use that have allowed the validation of complex models—namely, spheroids, tumouroids, hydrogel-embedded cultures (matrix-supported) and advanced bioengineered cultures assembled with bioprinting and microfluidics. This review is designed to present the state of advanced models of HGG, whilst focusing as much as is possible on the paediatric form of the disease. The reality remains, however, that paediatric HGG (pHGG) models are years behind those of adult HGG. Our goal is to bring this to light in the hope that pGBM models can be improved upon.

Highlights

Patients with high-grade glioma (HGG) brain tumours, including adult glioblastoma (GBM) and paediatric gliomas including paediatric GBM (PGBM) and diffuse midline glioma (DMG) have a five-year survival rate of 20% [1] and 5% [2], respectively
There is no standard chemotherapy regimen designed for paediatric HGG (PHGG) and patients are given radiotherapy and/or surgery on a case-by-case basis [4,5,6,7,8]—there is no evidence that Temozolomide is beneficial [7,9,10]
Previous models of diffuse intrinsic pontine glioma (DIPG) have suggested that cells disseminate throughout the pons both individually and collectively [19], this study investigated adult GBM lines injected into the pons and the implications for DMG remain to be confirmed

Summary

Introduction

Patients with high-grade glioma (HGG) brain tumours, including adult glioblastoma (GBM) and paediatric gliomas including paediatric GBM (PGBM) and diffuse midline glioma (DMG) have a five-year survival rate of 20% [1] and 5% [2], respectively. There is no standard chemotherapy regimen designed for paediatric HGG (PHGG) and patients are given radiotherapy and/or surgery on a case-by-case basis [4,5,6,7,8]—there is no evidence that Temozolomide is beneficial [7,9,10]. Previous models of diffuse intrinsic pontine glioma (DIPG) (recently reclassified as a subgroup of DMG) have suggested that cells disseminate throughout the pons both individually and collectively [19], this study investigated adult GBM lines injected into the pons and the implications for DMG remain to be confirmed. The inter- and intratumoural heterogeneity is extreme [21,22], resulting in inaccurate or misleading predictions of clinical response from simplified laboratory models—wasting precious time and resources

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