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Updated: Aug 22, 2025
A 3D Spheroid Model for Glioblastoma
Published on: April 9, 2020
Glioblastoma-Derived Three-Dimensional Ex Vivo Models to Evaluate Effects and Efficacy of Tumor Treating Fields
Vera Nickl1, Ellina Schulz1, Ellaine Salvador1
1Section Experimental Neurosurgery, Department of Neurosurgery, University of Würzburg, 97080 Würzburg, Germany.
Abstract:
Glioblastoma (GBM) displays a wide range of inter- and intra-tumoral heterogeneity contributing to therapeutic resistance and relapse. Although Tumor Treating Fields (TTFields) are effective for the treatment of GBM, there is a lack of ex vivo models to evaluate effects on patients' tumor biology or to screen patients for treatment efficacy. Thus, we adapted patient-derived three-dimensional tissue culture models to be compatible with TTFields application to tissue culture. Patient-derived primary cells (PDPC) were seeded onto murine organotypic hippocampal slice cultures (OHSC), and microtumor development with and without TTFields at 200 kHz was observed. In addition, organoids were generated from acute material cultured on OHSC and treated with TTFields. Lastly, the effect of TTFields on expression of the Ki67 proliferation marker was evaluated on cultured GBM slices. Microtumors exhibited increased sensitivity towards TTFields compared to monolayer cell cultures. TTFields affected tumor growth and viability, as the size of microtumors and the percentage of Ki67-positive cells decreased after treatment. Nevertheless, variability in the extent of the response was preserved between different patient samples. Therefore, these pre-clinical GBM models could provide snapshots of the tumor to simulate patient treatment response and to investigate molecular mechanisms of response and resistance.
Insights
New 3D models show Tumor Treating Fields (TTFields) effectively reduce glioblastoma (GBM) growth and proliferation in patient-derived cells, while preserving individual tumor response variability for personalized treatment insights.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Biomedical Engineering
Background:
- Glioblastoma (GBM) exhibits significant heterogeneity, leading to therapeutic resistance and recurrence.
- Current ex vivo models are insufficient for evaluating Tumor Treating Fields (TTFields) effects or screening patient responses.
- TTFields represent a promising therapeutic modality for GBM treatment.
Purpose of the Study:
- To develop and validate patient-derived 3D tissue culture models for TTFields application in glioblastoma.
- To assess the efficacy of TTFields on GBM microtumors and organoids.
- To investigate the impact of TTFields on GBM cell proliferation marker Ki67.
Main Methods:
- Adaptation of patient-derived primary cells (PDPC) onto murine organotypic hippocampal slice cultures (OHSC).
- Application of TTFields (200 kHz) to GBM microtumors and organoids cultured on OHSC.
- Evaluation of Ki67 proliferation marker expression post-TTFields treatment.
Main Results:
- GBM microtumors demonstrated enhanced sensitivity to TTFields compared to traditional monolayer cultures.
- TTFields treatment led to a reduction in microtumor size and Ki67-positive cell percentage, indicating decreased proliferation and improved viability.
- Variability in treatment response was observed across different patient-derived samples, mirroring clinical heterogeneity.
Conclusions:
- Developed 3D GBM models are suitable for simulating patient treatment responses to TTFields.
- These models offer a platform for investigating molecular mechanisms underlying TTFields response and resistance.
- The models hold potential for personalized medicine approaches in glioblastoma treatment.
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