Development of the Glioblastoma HiSpot®: A novel 3D culture model for the culture of primary human glioblastoma cells and microglia

Brown, Joanna 2019. Development of the Glioblastoma HiSpot®: A novel 3D culture model for the culture of primary human glioblastoma cells and microglia. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Glioblastoma(GBM)is a common and aggressive grade IV brain tumour with a prognosis of ~18 months. It is highlyheterogeneic between and within patients. Treatment options are limited and pharmaceutical interventions often fail at late stages of development, considered to result from poorly translatable models. GBM research has historically been performed using 2D, serum-cultured, established cell lines. These factors have been demonstrated to reduce the stem-like capacity and representativeness of the cancer cells. Animal and 3D models also lack the influence of microglia, which form a large bulk of the tumour mass and interact closely with GBM cells. The aim of this study was to demonstrate whether the 3D,air-liquid interface,primary human tissue reaggregation model known as the HiSpot® can be adapted for GBM. It established the ability of the HiSpot® to support tumour cells and microglia and determined how well the resulting cultures represent the general and patient specific features of GBM. The HiSpot® culture technique was optimised for the support of GBM tissue. HiSpots® were compared to patient and pathological data. Their response to chemotherapeutic treatment was recorded, and multiple biopsies were used from certain patients to investigate intra-tumour heterogeneity. HiSpots® can be cultured from primary GBM, in serum free, high density conditions, supporting tumour cells and microglia from each patient. The HiSpots® recapitulate patient-specific pathological features, and pharmacological sensitivity, and demonstrate variations in these features between different biopsy sites within each tumour. The HiSpot® is a suitable model for the culture of primary human GBM cells, which maintains the key relationship between tumour cells and microglia. HiSpots® are representative of patient-matched tumours and demonstrate the inter- and intra-tumour heterogeneity of GBM. The HiSpot® model can be used to improve the understanding of GBM and can be adapted for a number of potential research avenues.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	25 June 2020
Last Modified:	23 Jun 2021 02:05
URI:	https://orca.cardiff.ac.uk/id/eprint/132752

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