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Updated: Jun 4, 2025
Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived Glioblastoma Cells
Published on: August 24, 2018
Development of a hydrogel-based three-dimensional (3D) glioblastoma cell lines culture as a model system for CD73
Marjan Bahraminasab1, Samira Asgharzade2,3, Ali Doostmohamadi4
1Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Background:
Despite the development of various therapeutic approaches over the past decades, the treatment of glioblastoma multiforme (GBM) remains a major challenge. The extracellular adenosine-generating enzyme, CD73, is involved in the pathogenesis and progression of GBM, and targeting CD73 may represent a novel approach to treat this cancer. In this study, three-dimensional culture systems based on three hydrogel compositions were characterized and an optimal type was selected to simulate the GBM microenvironment. In addition, the effect of a CD73 inhibitor on GBM cell aggregates and spheroids was investigated as a potential therapeutic approach for this disease.
Methods:
Rheology measurements, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and cell proliferation assays were performed to analyze the synthesized hydrogel and select an optimal formulation. The viability of tumor cells in the optimal hydrogel was examined histologically and by confocal microscopy. In addition, the sensitivity of the tumor cells to the CD73 inhibitor was investigated using a cell proliferation assay and real-time PCR.
Results:
The data showed that the hydrogel containing 5 wt% gelatin and 5 wt% sodium alginate had better rheological properties and higher cell viability. Therefore, it could provide a more suitable environment for GBM cells and better mimic the natural microenvironment. GBM cells treated with CD73 inhibitors significantly decreased the proliferation rate and expression of VEGF and HIF1-α in the optimal hydrogel.
Conclusion:
Our current research demonstrates the great potential of CD73 inhibitor for clinical translation of cancer studies by analyzing the behavior and function of 3D tumor cells, and thus for more effective treatment protocols for GBM.
Insights
Targeting CD73 with inhibitors shows promise for glioblastoma multiforme (GBM) treatment. This study developed a 3D hydrogel model to test CD73 inhibitors, revealing reduced GBM cell proliferation and key marker expression.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Drug Discovery
Background:
- Glioblastoma multiforme (GBM) treatment remains challenging despite decades of therapeutic development.
- Extracellular adenosine-generating enzyme CD73 plays a role in GBM pathogenesis and progression.
- Targeting CD73 presents a novel therapeutic strategy for GBM.
Purpose of the Study:
- To characterize 3D culture systems using three hydrogel compositions to simulate the GBM microenvironment.
- To select an optimal hydrogel formulation for GBM research.
- To investigate the therapeutic potential of a CD73 inhibitor on GBM cell aggregates and spheroids.
Main Methods:
- Hydrogel characterization using rheology, FT-IR, and SEM.
- Cell viability assessment via histological and confocal microscopy.
- CD73 inhibitor efficacy evaluated through proliferation assays and real-time PCR.
Main Results:
- A hydrogel with 5 wt% gelatin and 5 wt% sodium alginate demonstrated optimal rheological properties and supported high cell viability, effectively mimicking the GBM microenvironment.
- CD73 inhibition significantly reduced GBM cell proliferation rates.
- Treatment with CD73 inhibitors led to decreased expression of VEGF and HIF1-α in GBM cells.
Conclusions:
- The developed 3D tumor cell model shows potential for clinical translation in cancer research.
- CD73 inhibitors hold promise for developing more effective glioblastoma treatment protocols.
