A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens

Kennedy, R.; Kuvshinov, D.; Sdrolia, A.; Kuvshinova, E.; Hilton, K.; Crank, S.; Beavis, A. W.; Green, V.; Greenman, J.

Abstract

Development of personalised cancer models to predict response to radiation would benefit patient care; particularly in malignancies where treatment resistance is prevalent. Herein, a robust, easy to use, tumour-on-a-chip platform which maintains precision cut head and neck cancer for the purpose of ex vivo irradiation is described. The device utilises sintered discs to separate the biopsy and medium, mimicking in vivo microvascular flow and diffusion, maintaining tissue viability for 68 h. Integrity of tissues is demonstrated by the low levels of lactate dehydrogenase release and retained histology, accompanied by assessment of cell viability by trypan blue exclusion and flow cytometry; fluid dynamic modelling validates culture conditions. An irradiation jig is described for reproducible delivery of clinically-relevant doses (5 × 2 Gy) to newly-presenting primary tumours (n = 12); the addition of concurrent cisplatin is also investigated (n = 8) with response analysed by immunohistochemistry. Fractionated irradiation reduced proliferation (BrdU, p = 0.0064), increased DNA damage (ƴH2AX, p = 0.0043) and caspase-dependent apoptosis (caspase-cleaved cytokeratin-18) compared to control; caspase-dependent apoptosis was further increased by concurrent cisplatin compared to control (p = 0.0063). This is a proof of principle study showing the response of cancer tissue to irradiation ex vivo in a bespoke system. The novel platform described has the potential to personalise treatment for patients in a cost-effective manner with applicability to any solid tumour.

Citation

Kennedy, R., Kuvshinov, D., Sdrolia, A., Kuvshinova, E., Hilton, K., Crank, S., Beavis, A. W., Green, V., & Greenman, J. (2019). A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens. Scientific reports, 9(1), Article 6327. https://doi.org/10.1038/s41598-019-42745-2

• Journal Article Type: Article
• Acceptance Date: Apr 1, 2019
• Online Publication Date: Apr 19, 2019
• Publication Date: Dec 1, 2019
• Deposit Date: Apr 24, 2019
• Publicly Available Date: Apr 25, 2019
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 6327
• DOI: https://doi.org/10.1038/s41598-019-42745-2
• Keywords: Experimental models of disease; Head and neck cancer
• Public URL: https://hull-repository.worktribe.com/output/1624413
• Publisher URL: https://www.nature.com/articles/s41598-019-42745-2
• Additional Information: Received: 26 October 2018; Accepted: 1 April 2019; First Online: 19 April 2019; : The authors declare no competing interests.
• Contract Date: Apr 24, 2019