Perfusion bioreactors are commonly used in normoxic conditions by tissue engineers to enable high density culture of cells on 3 dimensional substrates. Decellularised tissues of xenogenic origin offer a useful analogue for the tissues to which metastatic tumours would be expected to spread. This project will apply the tissue engineering and biomaterials expertise of co-I, Alastair Campbell-Ritchie, to develop bio-mimetic micro-environments for cancer research and the expertise of Nicola Everitt (Engineeting) in light sheet microscopy to image tumour growth and behaviour in real time.
Work item 1: To assess the efficacy of cancer cell colonisation on porous 3D-scaffolds in a continuously perfused bioreactor. Initial experiments will use highly metastatic breast cancer cells, MDA-MB-231, expressing fluorescent reporters. Cell survival, motility and colonisation will be assessed by fluorescent sheet microscopy in real time. PI Wheatley (Life Sciences, 60%), Ritchie (Engineering, 40%).
Work item 2: To determine cell viability during convective transfer from primary to secondary tumours. The bioreactor substrate will be seeded with a specified number of cells and culture medium sampled at intervals. The number of viable cells collected will be analysed using a clonogenic survival assay and morphological / biomarker expression.
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