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Article

Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

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Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
2
Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia
3
Innovation Center of the Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Academic Editor: Ashu Johri
Brain Sci. 2021, 11(8), 1025; https://doi.org/10.3390/brainsci11081025
Received: 12 June 2021 / Revised: 28 July 2021 / Accepted: 29 July 2021 / Published: 31 July 2021
Background: Various three-dimensional (3D) glioblastoma cell culture models have a limited duration of viability. Our aim was to develop a long-term 3D glioblastoma model, which is necessary for reliable drug response studies. Methods: Human U87 glioblastoma cells were cultured in alginate microfibers for 28 days. Cell growth, viability, morphology, and aggregation in 3D culture were monitored by fluorescent and confocal microscopy upon calcein-AM/propidium iodide (CAM/PI) staining every seven days. The glioblastoma 3D model was validated using temozolomide (TMZ) treatments 3 days in a row with a recovery period. Cell viability by MTT and resistance-related gene expression (MGMT and ABCB1) by qPCR were assessed after 28 days. The same TMZ treatment schedule was applied in 2D U87 cell culture for comparison purposes. Results: Within a long-term 3D model system in alginate fibers, U87 cells remained viable for up to 28 days. On day 7, cells formed visible aggregates oriented to the microfiber periphery. TMZ treatment reduced cell growth but increased drug resistance-related gene expression. The latter effect was more pronounced in 3D compared to 2D cell culture. Conclusion: Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization. View Full-Text
Keywords: glioblastoma; 3D cell culture; alginate hydrogel; temozolomide; drug resistance glioblastoma; 3D cell culture; alginate hydrogel; temozolomide; drug resistance
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MDPI and ACS Style

Dragoj, M.; Stojkovska, J.; Stanković, T.; Dinić, J.; Podolski-Renić, A.; Obradović, B.; Pešić, M. Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing. Brain Sci. 2021, 11, 1025. https://doi.org/10.3390/brainsci11081025

AMA Style

Dragoj M, Stojkovska J, Stanković T, Dinić J, Podolski-Renić A, Obradović B, Pešić M. Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing. Brain Sciences. 2021; 11(8):1025. https://doi.org/10.3390/brainsci11081025

Chicago/Turabian Style

Dragoj, Miodrag, Jasmina Stojkovska, Tijana Stanković, Jelena Dinić, Ana Podolski-Renić, Bojana Obradović, and Milica Pešić. 2021. "Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing" Brain Sciences 11, no. 8: 1025. https://doi.org/10.3390/brainsci11081025

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