Related Experiment Video
Updated: Jun 27, 2025
Author Spotlight: Developing Immunocompetent Organ-on-Chip Models for Infectious Disease Research
Published on: May 24, 2024
Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing
James I Kennedy1, Scott P Davies1, Peter W Hewett2
1Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Abstract:
Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.
Insights
Harnessing liver endothelial cells in an organ-on-a-chip model can enhance immune cell infiltration for hepatocellular cancer immunotherapy. This approach aims to overcome resistance and improve treatment efficacy for advanced liver tumors.
Area of Science:
- Hepatocellular Carcinoma Research
- Immunotherapy
- Organ-on-a-Chip Technology
Background:
- Immunotherapy, particularly checkpoint inhibitors, is standard for advanced hepatocellular cancer but faces significant resistance.
- The majority of patients with advanced liver tumors do not respond to current immunotherapy.
- Novel strategies are urgently needed to enhance the efficacy of immunotherapeutic agents.
Purpose of the Study:
- To investigate targeting liver endothelial cells to improve immune cell infiltration in hepatocellular cancer.
- To develop and validate an organ-on-a-chip model for studying immune cell interactions with liver endothelium.
- To establish a platform for testing new therapies and cell therapies for liver cancer.
Main Methods:
- Primary human liver endothelial cells were cultured using organ-on-a-chip technology.
- Peripheral blood mononuclear cells were perfused through the microfluidic system.
- Confocal and multiphoton imaging were employed to visualize immune cell capture and adhesion.
Main Results:
- Successful culture of primary human liver endothelial cells in an organ-on-a-chip system.
- Demonstrated capture and adhesion of immune cells in response to pro-inflammatory cytokines.
- Validated the model's ability to mimic immune cell interactions within the liver tumor microenvironment.
Conclusions:
- Organ-on-a-chip technology provides a viable platform for studying liver endothelial cell function in cancer.
- This model can be used to test therapies aimed at enhancing leukocyte infiltration for hepatocellular cancer.
- The platform is suitable for evaluating cell therapies, including CAR-T cells, for liver cancer treatment.
