Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-09686-0
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Funding
- National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs, UK) [NC/P002374/1]
- Cancer Research UK [A19277]
- Cancer Research UK Oxford Cancer Research Centre
- Cancer Research UK [19277] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/P002374/1] Funding Source: researchfish
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Pharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in-vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion is a vital factor for engineered human tissues to recapitulate key aspects of the tumour microenvironment. Organotypic culture and human tumour explants were allowed to grow long-term (14-35 days) and phenotypic features of perfused microtumours compared with those in the static culture. Differentiation status and therapeutic responses were significantly different under perfusion, indicating a distinct biological response of cultures grown under static conditions. Furthermore, heterogeneous co-culture of tumour and endothelial cells demonstrated selective cell-killing under therapeutic perfusion versus episodic delivery. We present a perfused 3D microtumour culture platform that sustains a more physiological tissue state and increased viability for long-term analyses. This system has the potential to tackle the disadvantages inherit of conventional pharmaceutical models and is suitable for precision medicine screening of tumour explants, particularly in hard-to-treat cancer types such as brain cancer which suffer from a lack of clinical samples.
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