Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues

Peng Liu; Sophie Roberts; James T Shoemaker; Jelena Vukasinovic; Darren C. Tomlinson; Valerie Speirs

doi:10.1371/journal.pone.0283044

Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues

Peng Liu^* (Corresponding Author), Sophie Roberts, James T Shoemaker, Jelena Vukasinovic, Darren C. Tomlinson, Valerie Speirs

^*Corresponding author for this work

University of Leeds

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Abstract

3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow. In this study, a three-dimensional scaffold, SeedEZ was applied within the PerfusionPal perfused culture system to investigate how perfusion, and blood-like oxygen delivery influenced breast cancer cell growth and their responses to a commonly used breast cancer drug tamoxifen. Our results showed that breast cancer cells could be maintained over 3 weeks in PerfusionPal with increased cell viability compared to static 3D culture in fully humanised conditions. This platform also supported examining the effect of tamoxifen on breast cancer cell lines and in primary patient-derived breast cancer samples. Future work is warranted to further the adaption for fully humanised assessment of drug effectiveness in a patient personalized approach with the aim to reduce the burden of animal use in cancer research and increase the degree of human pre-clinical data translation to clinic.

Original language	English
Article number	0283044
Number of pages	13
Journal	PloS ONE
Volume	18
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0283044
Publication status	Published - 16 Mar 2023

Bibliographical note

Open Access via the PLOS Agreement
Funding: This study was funded by NC3Rs studentship (NC/N00325X/1), NC3Rs/CRUK Skills and Capacity award (NC/T001259/1), the University of Aberdeen Development Trust, and the NIH SBIR Phase I and Phase II grants: 1R43TR001286, 2R44TR001286, and 5R44TR001286 awarded to Lena Biosciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data Availability Statement

All relevant data are within the manuscript and its Supporting Information files.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0283044Licence: CC BY

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Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 2.09 MBLicence: CC BY

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Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues. / Liu, Peng (Corresponding Author); Roberts, Sophie; Shoemaker, James T et al.
In: PloS ONE, Vol. 18, No. 3, 0283044, 16.03.2023.

Research output: Contribution to journal › Article › peer-review

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abstract = "3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow. In this study, a three-dimensional scaffold, SeedEZ was applied within the PerfusionPal perfused culture system to investigate how perfusion, and blood-like oxygen delivery influenced breast cancer cell growth and their responses to a commonly used breast cancer drug tamoxifen. Our results showed that breast cancer cells could be maintained over 3 weeks in PerfusionPal with increased cell viability compared to static 3D culture in fully humanised conditions. This platform also supported examining the effect of tamoxifen on breast cancer cell lines and in primary patient-derived breast cancer samples. Future work is warranted to further the adaption for fully humanised assessment of drug effectiveness in a patient personalized approach with the aim to reduce the burden of animal use in cancer research and increase the degree of human pre-clinical data translation to clinic.",

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Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues

Abstract

Bibliographical note

Data Availability Statement

UN SDGs

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