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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.

Authors

R. Kennedy

D. Kuvshinov

A. Sdrolia

E. Kuvshinova

K. Hilton

S. Crank

A. W. Beavis

V. Green



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., …Greenman, J. (2019). A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens. Scientific reports, 9(1), 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 Apr 19, 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 Multidisciplinary
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.

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.



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