| dc.description.abstract | Following the development of the lung-on-a-chip system there has been a rapid increase in interest in advanced tissue culture models embedded in microfluidic systems. Some models, and the focus of this thesis, utilise micro-structured compartments to control cell assembly and recapitulate tissue architecture. This thesis aims to develop a vascularised model of ovarian cancer within a microfluidic chip. Interactions between the vasculature and ovarian cancer have not been widely explored, though studies have demonstrated high micro-vessel density as an independent prognostic marker for worse progression-free survival in women with advanced epithelial ovarian cancer. In addition, the use of anti-angiogenics, such as bevacizumab, have been shown to be effective adjuvant and neoadjuvant therapies in high grade serous ovarian cancer (HGSOC) treatment. This thesis first examines the parameters enabling the formation of a reproducible stable microvascular system. Markers associated with the maturation of the microvasculture, including adheren and tight junction markers, are characterised, in addition to the quantification of the barrier properties of the endothelium. This system is then used to investigate the interactions between endothelial cells and various stromal cells potentially important for endothelium maturation. It is observed that pericytes inhibit vessel hyperplasia and reduce vessel permeability, in agreement with what is reported in literature, but also improve the stability of the vasculature in response to stress (low serum). The interaction between the vascular system and a HGSOC cell line (G33) is then presented. G33s are found to promote short-term vessel sprouting, whereas HUVECs were found to stimulate G33 proliferation and promote a change in morphology. Finally, our vascular model was used in developing a novel model for the assessment of efficacy of drug-therapy, via the embedding of G33 spheroids into a microvasculature. | en_US |
