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Updated: Jul 14, 2025
Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology
Published on: March 14, 2020
Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug
Ravi Jagatia1, Ewald J Doornebal1, Una Rastovic1
1The Roger Williams Institute of Hepatology, Foundation for Liver Research, 111, Coldharbour Lane, London SE5 9NT, United Kingdom; Faculty of Life Sciences and Medicine, King's College London, London WC2R 2LS, United Kingdom.
Background:
The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities.
Methods:
We used human precision-cut tissue slices (PCTS) derived from resected tumours to create a patient-specific immunocompetent disease model that captures the multifaceted and intricate heterogeneity of the tumour and the tumour microenvironment. Tissue architecture, tumour viability and treatment response to single agent and combination therapies were assessed longitudinally over 8 days of ex vivo culture by histological analysis, detection of proliferation/cell death markers, ATP content via HPLC. Immune cell infiltrate was assessed using PCR and immunofluorescence. Checkpoint receptor expression was quantified via Quantigene RNA assay.
Findings:
After optimising the culture conditions, PCTS maintained the original tissue architecture, including tumour morphology, stroma and tumour-infiltrated leukocytes. Moreover, PCTS retained the tumour-specific immunophenotype over time, suggesting the utility of PCTS to investigate immunotherapeutic drug efficacy and identify non-responsiveness.
Interpretation:
Here we have characterised the PCTS model and demonstrated its effectiveness as a robust preclinical tool that will significantly support the development of successful (immuno)therapeutic strategies for PLC.
Funding:
Foundation for Liver Research, London.
Insights
A new patient-specific immunocompetent model using human precision-cut tissue slices (PCTS) effectively mimics primary liver cancer (PLC) and its microenvironment. This robust preclinical tool aids in developing novel immunotherapies for PLC.
Area of Science:
- Oncology
- Immunology
- Preclinical Research
Background:
- Immunomodulatory therapies have transformed primary liver cancer (PLC) treatment, yet preclinical models face challenges.
- There is a critical need for new, immunologically relevant PLC models to advance translational research and personalized medicine.
Purpose of the Study:
- To develop and characterize a patient-specific immunocompetent disease model for primary liver cancer (PLC).
- To assess the utility of this model for evaluating immunotherapeutic strategies and drug discovery.
Main Methods:
- Human precision-cut tissue slices (PCTS) from resected PLC tumors were cultured ex vivo.
- Longitudinal assessment of tissue architecture, viability, immune cell infiltrate, and response to therapies over 8 days.
- Analysis included histology, proliferation/cell death markers, ATP content, PCR, immunofluorescence, and checkpoint receptor expression.
Main Results:
- Optimized PCTS cultures maintained original tissue architecture, including tumor morphology, stroma, and leukocytes.
- The model retained tumor-specific immunophenotype during culture, demonstrating its suitability for immunotherapy studies.
- PCTS proved effective in investigating immunotherapeutic drug efficacy and identifying non-responders.
Conclusions:
- The characterized PCTS model is a robust preclinical tool for primary liver cancer (PLC) research.
- This model will significantly support the development of effective immunotherapeutic strategies for PLC.
- It aids in predicting treatment response and advancing personalized medicine approaches.
