---
title: "Patient-derived ex vivo model of cholangiocarcinoma using precision-cut tissue slices"
id: "biorxiv-4-a-patient-derived-ex-vivo-tissue-model-of-cholangiocarcinoma-using-precision"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-a-patient-derived-ex-vivo-tissue-model-of-cholangiocarcinoma-using-precision"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.17.745977v1?rss=1"
published_at: "2026-09-18T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Patient-derived ex vivo model of cholangiocarcinoma using precision-cut tissue slices
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-a-patient-derived-ex-vivo-tissue-model-of-cholangiocarcinoma-using-precision
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.17.745977v1?rss=1)
- **Published At:** 2026-09-18T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study developed a patient-derived ex vivo model of **cholangiocarcinoma** using **precision-cut tissue slices (PCTS)** generated from surgical specimens collected from 25 patients (2022–2024). - PCTS were cultured up to 15 days with serial assessment of viability and histological architecture; viability was maintained to Day 15 with no significant reduction from baseline. - Tumour features were retained in culture, including architecture, **cytokeratin-19** positivity, and resident immune cells (CD3+ T cells and CD68+ macrophages). - Quantitative proteomics (SWATH-DIA) measured 4,578 proteins at Days 0, 3, 7 and 15 and revealed a staged proteomic response to ex vivo culture. - Differentially abundant proteins rose over time: 8 proteins at Day 3, 127 at Day 7, and 180 at Day 15, then stabilised; changes included early loss of inflammatory and stromal proteins, ongoing cellular stress responses, and metabolic reprogramming. - Proteomic signatures specific to CCA subtypes were preserved across the culture period. - Pharmacological testing showed dose-dependent cytotoxicity with staurosporine; responses to clinically relevant chemotherapy (5'-deoxy-5-fluorouridine, gemcitabine ± cisplatin) were variable across slices. - The model is presented as a platform that preserves tumour microenvironment features and subtype identity for at least 15 days and can be used for ex vivo therapeutic evaluation. - Funding sources included the National Centre for the Replacement Refinement and Reduction of Animals in Research and North West Cancer Research; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices | bioRxiv Skip to main content New Results A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices View ORCID Profile Timothy M Gilbert , View ORCID Profile Owen McGreevy , View ORCID Profile Maria-Danae Jessel , Roz Jenkins , Mohamed Bosakhar , Marc Quinn , View ORCID Profile Lawrence O'Leary , View ORCID Profile Anthony Evans , Timothy Andrews , Rafael Diaz-Nieto , Robert P Jones , View ORCID Profile Stephen Fenwick , View ORCID Profile William Greenhalf , Daniel Palmer , Hassan Z Malik , View ORCID Profile Christopher Goldring , View ORCID Profile Laura Randle doi: https://doi.org/10.64898/2026.09.17.745977 Timothy M Gilbert 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Timothy M Gilbert Owen McGreevy 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Owen McGreevy Maria-Danae Jessel 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Maria-Danae Jessel Roz Jenkins 2 CDSS Bioanalytical Facility, University of Liverpool, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mohamed Bosakhar 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marc Quinn 3 Liverpool University Hospitals NHS Foundation Trust, Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lawrence O'Leary 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lawrence O'Leary Anthony Evans 4 Computational Biology Facility, University of Liverpool, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Anthony Evans Timothy Andrews 3 Liverpool University Hospitals NHS Foundation Trust, Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rafael Diaz-Nieto 5 Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Robert P Jones 5 Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Stephen Fenwick 6 Liverpool University Hospitals NHS Foundation Trust; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stephen Fenwick William Greenhalf 7 University of Liverpool`; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for William Greenhalf Daniel Palmer 8 Clatterbridge Cancer Centre, Liverpool, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hassan Z Malik 3 Liverpool University Hospitals NHS Foundation Trust, Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Christopher Goldring 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christopher Goldring Laura Randle 1 University of Liverpool; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Laura Randle For correspondence: lerandle{at}liverpool.ac.uk Abstract Info/History Metrics Supplementary material Preview PDF 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, Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Centre for the Replacement Refinement and Reduction of Animals in Research, https://ror.org/02w0kg036 , NC/X001679 North West Cancer Research, https://ror.org/025qv0671 , PHD2022.03 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted September 18, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices Timothy M Gilbert , Owen McGreevy , Maria-Danae Jessel , Roz Jenkins , Mohamed Bosakhar , Marc Quinn , Lawrence O'Leary , Anthony Evans , Timothy Andrews , Rafael Diaz-Nieto , Robert P Jones , Stephen Fenwick , William Greenhalf , Daniel Palmer , Hassan Z Malik , Christopher Goldring , Laura Randle bioRxiv 2026.09.17.745977; doi: https://doi.org/10.64898/2026.09.17.745977 Share This Article: Copy Citation Tools A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices Timothy M Gilbert , Owen McGreevy , Maria-Danae Jessel , Roz Jenkins , Mohamed Bosakhar , Marc Quinn , Lawrence O'Leary , Anthony Evans , Timothy Andrews , Rafael Diaz-Nieto , Robert P Jones , Stephen Fenwick , William Greenhalf , Daniel Palmer , Hassan Z Malik , Christopher Goldring , Laura Randle bioRxiv 2026.09.17.745977; doi: https://doi.org/10.64898/2026.09.17.745977 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8010) Biochemistry (18733) Bioengineering (14876) Bioinformatics (44392) Biophysics (22588) Cancer Biology (19713) Cell Biology (26896) Clinical Trials (138) Developmental Biology (13961) Ecology (21001) Epidemiology (2067) Evolutionary Biology (25436) Genetics (16162) Genomics (23498) Immunology (18693) Microbiology (42451) Molecular Biology (18054) Neuroscience (93419) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5092) Physiology (8111) Plant Biology (15997) Scientific Communication and Education (2095) Synthetic Biology (4559) Systems Biology (10233) Zoology (2389)
## Related Clinical Research

- [Vitamin D (VDR/RXR) signaling limits platinum-induced ovarian cancer stem cell plasticity](https://medichelpline.com/clinical-feed/biorxiv-6-activation-of-vitamin-d-signaling-suppresses-platinum-induced-ovarian-cancer.md)
- [Inhibiting the MAT2A–SAM Axis Enhances Platinum Sensitivity in Ovarian Cancer by Disrupting DNA Re](https://medichelpline.com/clinical-feed/biorxiv-9-targeting-mat2a-s-adenosylmethionine-sam-axis-attenuates-dna-damage-response.md)
- [Trastuzumab + nivolumab with gemcitabine–cisplatin as first-line therapy for HER2-positive unresec](https://medichelpline.com/clinical-feed/nature-3-trastuzumab-plus-nivolumab-with-gemcitabine-and-cisplatin-as-first-line-therapy.md)
- [Long-Term Follow-Up of JCOG1008: 3-Weekly vs Weekly Cisplatin Chemoradiotherapy in Postoperative H](https://medichelpline.com/clinical-feed/pubmed-42361282.md) (DOI: 10.1200/JCO-25-01708)
- [PAX9 drives lethal autophagy and EGFR degradation to limit survival in oral squamous cell carcinoma](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-pax9-activates-autophagy-through-a-transcription-dependent-mechanism-promoting.md)

## Navigation
- [← Back to Oncology Feed](https://medichelpline.com/clinical-feed/oncology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.