A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices
- 1University of Liverpool
Abstract
Background & Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor five-year survival. Improving outcomes requires preclinical models that faithfully recapitulate the native tumour microenvironment. Precision-Cut Tissue Slices (PCTS) retain in-vivo architecture and represent a promising candidate. We aimed to establish a patient-derived PCTS model of CCA, characterise its response to ex-vivo culture, and assess its use as a platform for therapeutic testing. Methods: PCTS were generated from 25 patients undergoing curative-intent resection for presumed CCA (2022-2024) and cultured for up to 15 days. Viability and histological architecture were assessed serially. Quantitative proteomics (SWATH-DIA) was performed at Days 0, 3, 7 and 15. A subset were treated with staurosporine or clinically relevant chemotherapy (5'-deoxy-5-fluorouridine, gemcitabine {+/-} cisplatin). Results: PCTS viability was maintained to Day 15, with no significant reduction from baseline. PCTS retain tumour architecture, cytokeratin-19-positivity and resident CD3+/CD68+ immune cells during culture. Proteomic profiling quantified 4,578 proteins and identified a staged response, with differentially abundant proteins increasing from 8 (Day 3) to 127 (Day 7) and 180 (Day 15), stabilising thereafter. This comprised of an early loss of inflammatory and stromal proteins, sustained cellular stress responses and metabolic reprogramming. CCA subtype-specific proteomic signatures were preserved throughout culture. Staurosporine produced dose-dependent cytotoxicity whilst chemotherapy responses were variable. Conclusions: Patient-derived CCA PCTS maintain viability, tumour architecture and subtype identity for 15 days while undergoing a defined proteomic response to culture, and retain pharmacological responsiveness,
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BibTeX
@misc{gilbert2026patientderived,
title = {{A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices}},
author = {T. M. Gilbert and O. McGreevy and M.-D. Jessel and R. Jenkins and M. Bosakhar and M. Quinn and L. O'Leary and A. Evans and T. Andrews and R. Diaz-Nieto and R. P. Jones and S. Fenwick and W. Greenhalf and D. Palmer and H. Z. Malik and C. Goldring and L. Randle},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.745977},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.745977v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices
AU - T. M. Gilbert
AU - O. McGreevy
AU - M.-D. Jessel
AU - R. Jenkins
AU - M. Bosakhar
AU - M. Quinn
AU - L. O'Leary
AU - A. Evans
AU - T. Andrews
AU - R. Diaz-Nieto
AU - R. P. Jones
AU - S. Fenwick
AU - W. Greenhalf
AU - D. Palmer
AU - H. Z. Malik
AU - C. Goldring
AU - L. Randle
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.745977
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.745977v1
AB - Background & Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor five-year survival. Improving outcomes requires preclinical models that faithfully recapitulate the native tumour microenvironment. Precision-Cut Tissue Slices (PCTS) retain in-vivo architecture and represent a promising candidate. We aimed to establish a patient-derived PCTS model of CCA, characterise its response to ex-vivo culture, and assess its use as a platform for therapeutic testing. Methods: PCTS were generated from 25 patients undergoing curative-intent resection for presumed CCA (2022-2024) and cultured for up to 15 days. Viability and histological architecture were assessed serially. Quantitative proteomics (SWATH-DIA) was performed at Days 0, 3, 7 and 15. A subset were treated with staurosporine or clinically relevant chemotherapy (5'-deoxy-5-fluorouridine, gemcitabine {+/-} cisplatin). Results: PCTS viability was maintained to Day 15, with no significant reduction from baseline. PCTS retain tumour architecture, cytokeratin-19-positivity and resident CD3+/CD68+ immune cells during culture. Proteomic profiling quantified 4,578 proteins and identified a staged response, with differentially abundant proteins increasing from 8 (Day 3) to 127 (Day 7) and 180 (Day 15), stabilising thereafter. This comprised of an early loss of inflammatory and stromal proteins, sustained cellular stress responses and metabolic reprogramming. CCA subtype-specific proteomic signatures were preserved throughout culture. Staurosporine produced dose-dependent cytotoxicity whilst chemotherapy responses were variable. Conclusions: Patient-derived CCA PCTS maintain viability, tumour architecture and subtype identity for 15 days while undergoing a defined proteomic response to culture, and retain pharmacological responsiveness,
ER -