Development of a hydrogel-based three-dimensional (3D) glioblastoma cell lines culture as a model system for CD73 inhibitor response study

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 re...

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Veröffentlicht in:	Biomedical engineering online Jg. 23; H. 1; S. 127 - 23
Hauptverfasser:	Bahraminasab, Marjan, Asgharzade, Samira, Doostmohamadi, Ali, Satari, Atefeh, Hasannejad, Farkhonde, Arab, Samaneh
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 21.12.2024 BioMed Central Ltd Springer Nature B.V BMC
Schlagworte:	3D cell culture 5'-Nucleotidase - antagonists & inhibitors 5'-Nucleotidase - metabolism Adenosine Alginates - chemistry Alginates - pharmacology Alginic acid Angiogenesis Biocompatibility Biodegradation Biomaterials Biomedical Engineering and Bioengineering Biomedical Engineering/Biotechnology Biomedical materials Biotechnology Brain cancer Cancer Cancer therapies CD73 antigen CD73 inhibitor Cell culture Cell Culture Techniques, Three Dimensional Cell Line, Tumor Cell lines Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Cell viability Colloids Confocal microscopy Drug therapy Engineering Enzyme inhibitors Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Fourier transforms Gelatin Gelatin–alginate hydrogel Glioblastoma Glioblastoma - drug therapy Glioblastoma - metabolism Glioblastoma - pathology Glioblastoma multiforme Glioma GPI-Linked Proteins Health services Humans Hydrogels Hydrogels - chemistry Hydrogels - pharmacology Hypoxia Infrared analysis Infrared spectroscopy Inhibitors Medical prognosis Metastasis Microenvironments Microscopy Pathogenesis Patients Pharmaceuticals Polymers Real time Rheological properties Rheology Scanning electron microscopy Sodium Sodium alginate Spheroids Testing Tumor cells Tumor Microenvironment - drug effects Tumors Vascular endothelial growth factor Iran CD73 inhibitor 3D cell culture Glioblastoma Gelatin–alginate hydrogel
ISSN:	1475-925X, 1475-925X
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1475-925X 1475-925X
DOI:	10.1186/s12938-024-01320-1