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A novel microfluidic device capable of maintaining functional thyroid carcinoma

Riley, Andrew; Green, Victoria; V, Green; Cheah, Ramsah; McKenzie, Gordon; Karsai, Laszlo; England, James; Greenman, John

Authors

Andrew Riley

Victoria Green

Green V

Ramsah Cheah

Gordon McKenzie

Laszlo Karsai

James England



Abstract

Background
Though the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or ‘precision’ medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies.

Methods
Human thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 μm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting).

Results
Maintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p 

Journal Article Type Article
Publication Date Mar 22, 2019
Journal BMC cancer
Print ISSN 1471-2407
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 19
Article Number 259
Institution Citation Riley, A., Green, V., Cheah, R., McKenzie, G., Karsai, L., England, J., & Greenman, J. (2019). A novel microfluidic device capable of maintaining functional thyroid carcinoma. BMC Cancer, 19, https://doi.org/10.1186/s12885-019-5465-z
DOI https://doi.org/10.1186/s12885-019-5465-z
Keywords Thyroid gland; Microfluidics; Viability; De-differentiation; Radioiodine therapy
Publisher URL https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5465-z

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