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Updated: Jan 16, 2026
Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
Published on: August 16, 2020
Novel Diffuse Midline Glioma-on-Chip Recapitulating Tumor Biophysical Microenvironment to Assess the Heterogeneity of
Lisa Terrassoux1,2, Calypso Hazard1,2, Agathe Laratte1,2
1Université Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, F-59000, France.
Abstract:
Despite significant efforts, Diffuse Midline Gliomas (DMGs) remain incurable. Although promising results are obtained in preclinical studies, most approaches have failed to improve survival in these young patients. In this context, by integrating elements of the biophysical tumor microenvironment known to regulate the response to therapies, a new preclinical tool is developed to better evaluate the efficacy of antitumoral strategies. For this purpose, a novel DMG-on-Chip (DoC) is engineered composed of a 3D dense tumor disk embedded in an extracellular matrix, which is accessible for real-time monitoring using wide-field phase contrast or confocal fluorescence microscopy. By driving the oxygen supply within the chip solely in a radial manner, a hypoxia gradient is established that can be associated with changes in DMG cell phenotype, proliferation, and rewiring of metabolic and stress transcriptomic signatures. Finally, DoC is used to analyze the spatial heterogeneity of the response of DMG cell lines and patient-derived 3D cultures to treatments through cell segmentation. Altogether, these interdisciplinary characterizations validate the new tool as an interesting healthcare solution to understand how cell responses are modulated by biophysical or biochemical cues in the tumor microenvironment.
Insights
Researchers developed a novel Diffuse Midline Glioma-on-Chip (DoC) model. This tool integrates biophysical cues to better assess anti-cancer strategies and understand treatment responses in the tumor microenvironment.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Biology
Background:
- Diffuse Midline Gliomas (DMGs) are aggressive brain tumors with poor prognosis.
- Current preclinical models often fail to predict clinical efficacy of anti-cancer therapies.
- Understanding the tumor microenvironment's role in therapy response is crucial.
Purpose of the Study:
- To develop a novel preclinical tool for evaluating anti-DMG therapeutic strategies.
- To investigate the impact of biophysical cues, specifically hypoxia gradients, on DMG behavior.
- To analyze spatial heterogeneity in treatment response within a 3D DMG model.
Main Methods:
- Engineered a DMG-on-Chip (DoC) model with a 3D tumor disk in an extracellular matrix.
- Established a radial oxygen supply to create a hypoxia gradient.
- Utilized microscopy for real-time monitoring and cell segmentation for response analysis.
Main Results:
- The DoC model successfully established a hypoxia gradient, influencing DMG cell phenotype, proliferation, and transcriptomic signatures.
- Spatial heterogeneity of treatment responses in DMG cell lines and patient-derived cultures was analyzed.
- The model demonstrated the modulation of cell responses by biophysical and biochemical cues.
Conclusions:
- The developed DMG-on-Chip (DoC) is a validated preclinical tool for assessing anti-cancer strategies.
- This model aids in understanding how tumor microenvironment cues affect DMG cell responses to therapy.
- The DoC offers a promising healthcare solution for advancing DMG research.
