Dragoj, Miodrag

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  • Dragoj, Miodrag (2)
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Author's Bibliography

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

Dragoj, Miodrag; Stojkovska, Jasmina; Stankovic, Tijana; Dinic, Jelena; Podolski-Renic, Ana; Obradović, Bojana; Pesic, Milica

(2021)

TY  - 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 . .
1
15
10

Development of 3D microenvironment for engineering of glioblastoma brain tumor

Stojkovska, Jasmina; Stanković, Tijana; Dragoj, Miodrag; Petrović, Jelena; Radonjić, Mia; Pešić, Milica; Obradović, Bojana

(2021)

TY  - CONF
AU  - Stojkovska, Jasmina
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Petrović, Jelena
AU  - Radonjić, Mia
AU  - Pešić, Milica
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6353
AB  - The aim of this work was to develop a 3D microenvironment for glioblastoma brain tumor engineering based on alginate
hydrogels as a matrix for cell immobilization followed by cultivation in a biomimetic perfusion bioreactor. Alginate
microfibers with immobilized cells were obtained by a simple extrusion technique. We have examined the influence of the
needle diameter (22G - 28G), cell density in alginate solution (1 x 106 - 8 x 106 cells/ml) and different cancer cell lines (rat
C6 and human U251 and U87) on cell immobilization efficiency and viability. The best alginate microfibers (500 µm in
diameter) with all immobilized cells were obtained by applying a 25G needle with a minimal cell density of 4 x 106 cells/ml.
The obtained microfibers with immobilized cells (C6 and U87) were cultivated in a perfusion bioreactor at the continuous
medium flowrate in the range 0.05-0.30 ml/min over short- and long-term cultivation periods. The results have shown that
the flowrate of 0.30 ml/min, corresponding to the superficial velocity of 100 µm/s, in combination with the C6 cell density
of 8 x 106 cells/ml in short-term studies yielded higher cell viabilities and proliferation as compared to the control static
culture. In addition, U87 cells immobilized in alginate microfibers at the density of 4 x 106 cells/ml after long-term
cultivation at the medium flowrate of 0.05 ml/min (superficial velocity of 15 µm/s) stayed viable.
The overall results have shown potentials of the applied approach for tumor engineering provided optimization of
cultivation conditions for each cell type.
C3  - 6th World TERMIS Conference 2021 Abstract Book
T1  - Development of 3D microenvironment for engineering of glioblastoma brain tumor
SP  - 930
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6353
ER  - 
@conference{
author = "Stojkovska, Jasmina and Stanković, Tijana and Dragoj, Miodrag and Petrović, Jelena and Radonjić, Mia and Pešić, Milica and Obradović, Bojana",
year = "2021",
abstract = "The aim of this work was to develop a 3D microenvironment for glioblastoma brain tumor engineering based on alginate
hydrogels as a matrix for cell immobilization followed by cultivation in a biomimetic perfusion bioreactor. Alginate
microfibers with immobilized cells were obtained by a simple extrusion technique. We have examined the influence of the
needle diameter (22G - 28G), cell density in alginate solution (1 x 106 - 8 x 106 cells/ml) and different cancer cell lines (rat
C6 and human U251 and U87) on cell immobilization efficiency and viability. The best alginate microfibers (500 µm in
diameter) with all immobilized cells were obtained by applying a 25G needle with a minimal cell density of 4 x 106 cells/ml.
The obtained microfibers with immobilized cells (C6 and U87) were cultivated in a perfusion bioreactor at the continuous
medium flowrate in the range 0.05-0.30 ml/min over short- and long-term cultivation periods. The results have shown that
the flowrate of 0.30 ml/min, corresponding to the superficial velocity of 100 µm/s, in combination with the C6 cell density
of 8 x 106 cells/ml in short-term studies yielded higher cell viabilities and proliferation as compared to the control static
culture. In addition, U87 cells immobilized in alginate microfibers at the density of 4 x 106 cells/ml after long-term
cultivation at the medium flowrate of 0.05 ml/min (superficial velocity of 15 µm/s) stayed viable.
The overall results have shown potentials of the applied approach for tumor engineering provided optimization of
cultivation conditions for each cell type.",
journal = "6th World TERMIS Conference 2021 Abstract Book",
title = "Development of 3D microenvironment for engineering of glioblastoma brain tumor",
pages = "930",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6353"
}
Stojkovska, J., Stanković, T., Dragoj, M., Petrović, J., Radonjić, M., Pešić, M.,& Obradović, B.. (2021). Development of 3D microenvironment for engineering of glioblastoma brain tumor. in 6th World TERMIS Conference 2021 Abstract Book, 930.
https://hdl.handle.net/21.15107/rcub_technorep_6353
Stojkovska J, Stanković T, Dragoj M, Petrović J, Radonjić M, Pešić M, Obradović B. Development of 3D microenvironment for engineering of glioblastoma brain tumor. in 6th World TERMIS Conference 2021 Abstract Book. 2021;:930.
https://hdl.handle.net/21.15107/rcub_technorep_6353 .
Stojkovska, Jasmina, Stanković, Tijana, Dragoj, Miodrag, Petrović, Jelena, Radonjić, Mia, Pešić, Milica, Obradović, Bojana, "Development of 3D microenvironment for engineering of glioblastoma brain tumor" in 6th World TERMIS Conference 2021 Abstract Book (2021):930,
https://hdl.handle.net/21.15107/rcub_technorep_6353 .