In vitro modelling of human glioblastoma migration and angiogenesis
type: CreativeWork
description: Glioblastoma (GBM) invasion and angiogenesis are critical for the tumour's fast growth and recurrence. A significant limitation in the development of innovative anti-invasive and anti-angiogenic treatments is the lack of personalised in vitro experimental models to accurately recreate the physiological and pathophysiological properties of the brain. This project focuses on the development of an injury-free ‘wound healing’ and a vascularised tumoroid in vitro model using patient-derived GBM cells. These models are used to recapitulate how individual components of the GBM's complex brain microenvironment, such as low oxygen tension (e.g. 1% O2), vasculature related stromal cells (e.g. human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HDF)) and growth factors (e.g. VEGF, bFGF), support the GBM migration and angiogenesis. In the first half of the thesis, an injury-free ‘wound healing’ model was developed that aimed at introducing an accurately defined cell-free area on a confluent GBM monolayer to investigate GBM migration in 2D. The cells became progressively motile perpendicularly to the border. Quantitative results were reported by mapping the velocity field of collectively migrating cells using particle image velocimetry. Hypoxia (1% O2) showed a higher average cell velocity and polar order parameter (meaning that the cells move more in the outward direction normal to the initial border) compared to normoxia (20% O2). Replacing one side of the ‘wound’ with a HUVECs monolayer was also found to increase the GBM average cell velocity and polar order parameter. These results are consistent with in vivo observations of hypoxia promoting GBM invasion and blood vessels chemotactically attracting GBM cells. In the second half of the thesis, a GBM vascularised tumouroid model was developed to investigate GBM angiogenesis in 3D by embeddeding GBM/HUVECs spheroids in HDF containing fibrin gel. Co-culturing HUVECs with HDF lead to HUVECs undergoing an a…
abstract: Glioblastoma (GBM) invasion and angiogenesis are critical for the tumour's fast growth and recurrence. A significant limitation in the development of innovative anti-invasive and anti-angiogenic treatments is the lack of personalised in vitro experimental models to accurately recreate the physiological and pathophysiological properties of the brain. This project focuses on the development of an injury-free ‘wound healing’ and a vascularised tumoroid in vitro model using patient-derived GBM cells. These models are used to recapitulate how individual components of the GBM's complex brain microenvironment, such as low oxygen tension (e.g. 1% O2), vasculature related stromal cells (e.g. human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HDF)) and growth factors (e.g. VEGF, bFGF), support the GBM migration and angiogenesis. In the first half of the thesis, an injury-free ‘wound healing’ model was developed that aimed at introducing an accurately defined cell-free area on a confluent GBM monolayer to investigate GBM migration in 2D. The cells became progressively motile perpendicularly to the border. Quantitative results were reported by mapping the velocity field of collectively migrating cells using particle image velocimetry. Hypoxia (1% O2) showed a higher average cell velocity and polar order parameter (meaning that the cells move more in the outward direction normal to the initial border) compared to normoxia (20% O2). Replacing one side of the ‘wound’ with a HUVECs monolayer was also found to increase the GBM average cell velocity and polar order parameter. These results are consistent with in vivo observations of hypoxia promoting GBM invasion and blood vessels chemotactically attracting GBM cells. In the second half of the thesis, a GBM vascularised tumouroid model was developed to investigate GBM angiogenesis in 3D by embeddeding GBM/HUVECs spheroids in HDF containing fibrin gel. Co-culturing HUVECs with HDF lead to HUVECs undergoing an a…
author: Stavropoulou-Tatla, Agavi
language: eng
keywords: glioblastoma, migration, angiogenesis
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/afcb0906-0020-45fe-847e-186ca81a69c4/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020
date modified: 2026-07-22T22:24:16Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.66611