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
2021
Authors
Dragoj, MiodragStojkovska, Jasmina
Stankovic, Tijana
Dinic, Jelena
Podolski-Renic, Ana
Obradović, Bojana
Pesic, Milica
Article (Published version)
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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 micro...fiber 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.
Keywords:
glioblastoma / 3D cell culture / alginate hydrogel / temozolomide / drug resistanceSource:
Brain Sciences, 2021, 11, 8Funding / projects:
DOI: 10.3390/brainsci11081025
ISSN: 2076-3425
PubMed: 34439644
WoS: 000688937200001
Scopus: 2-s2.0-85112073527
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Tehnološko-metalurški fakultetTY - JOUR AU - Dragoj, Miodrag AU - Stojkovska, Jasmina AU - Stankovic, Tijana AU - Dinic, Jelena AU - Podolski-Renic, Ana AU - Obradović, Bojana AU - Pesic, Milica PY - 2021 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4783 AB - 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. T2 - Brain Sciences T1 - 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 IS - 8 VL - 11 DO - 10.3390/brainsci11081025 ER -
@article{ author = "Dragoj, Miodrag and Stojkovska, Jasmina and Stankovic, Tijana and Dinic, Jelena and Podolski-Renic, Ana and Obradović, Bojana and Pesic, Milica", year = "2021", abstract = "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.", journal = "Brain Sciences", title = "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", number = "8", volume = "11", doi = "10.3390/brainsci11081025" }
Dragoj, M., Stojkovska, J., Stankovic, T., Dinic, J., Podolski-Renic, A., Obradović, B.,& Pesic, M.. (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. in Brain Sciences, 11(8). https://doi.org/10.3390/brainsci11081025
Dragoj M, Stojkovska J, Stankovic T, Dinic J, Podolski-Renic A, Obradović B, Pesic 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. in Brain Sciences. 2021;11(8). doi:10.3390/brainsci11081025 .
Dragoj, Miodrag, Stojkovska, Jasmina, Stankovic, Tijana, Dinic, Jelena, Podolski-Renic, Ana, Obradović, Bojana, Pesic, Milica, "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" in Brain Sciences, 11, no. 8 (2021), https://doi.org/10.3390/brainsci11081025 . .