TY  - JOUR
AU  - Milanović, Marijana
AU  - Bekić, Marina
AU  - Đokić, Jelena
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
PY  - 2024
UR  - https://www.ijbs.com/v20p1064.htm
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2313
AB  - Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to induce Th1 cells. However, αKG also promoted IL-1β secretion by mature moDCs, despite inflammasome downregulation, potentiating their Th17 polarizing capacity. αKG induced the expression of anti-oxidative enzymes and hypoxia-induced factor (HIF)-1α in moDCs, activated Akt/FoxO1 pathway and increased autophagy flux, oxidative phosphorylation (OXPHOS) and glycolysis. This correlated with a higher capacity of immature αKG-moDCs to induce Th2 cells, and conventional regulatory T cells in an indolamine-dioxygenase (IDO)-1-dependent manner. Additionally, αKG increased moDCs’ capacity to induce non-conventional T regulatory (Tr)-1 and IL-10-producing CD8+T cells via up-regulated immunoglobulin-like transcript (ILT3) expression in OXPHOS-dependent manner. These results suggested that exogenous αKG-altered redox metabolism in moDCs contributed to their tolerogenic properties, which could be relevant for designing more efficient therapeutic approaches in DCs-mediated immunotherapies.
PB  - Ivyspring International
T2  - International Journal of Biological Sciences
T2  - International Journal of Biological Sciences
T1  - Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response
EP  - 1087
IS  - 3
SP  - 1064
VL  - 20
DO  - 10.7150/ijbs.91109
ER  - 

@article{
author = "Milanović, Marijana and Bekić, Marina and Đokić, Jelena and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej",
year = "2024",
abstract = "Alpha-ketoglutarate (αKG) emerged as a key regulator of energetic and redox metabolism in cells, affecting the immune response in various conditions. However, it remained unclear how the exogenous αKG modulates the functions of dendritic cells (DCs), key cells regulating T-cell response. Here we found that non-toxic doses of αKG display anti-inflammatory properties in human APC-T cell interaction models. In a model of monocyte-derived (mo)DCs, αKG impaired the differentiation, and the maturation of moDCs induced with lipopolysaccharide (LPS)/interferon (IFN)-γ, and decreased their capacity to induce Th1 cells. However, αKG also promoted IL-1β secretion by mature moDCs, despite inflammasome downregulation, potentiating their Th17 polarizing capacity. αKG induced the expression of anti-oxidative enzymes and hypoxia-induced factor (HIF)-1α in moDCs, activated Akt/FoxO1 pathway and increased autophagy flux, oxidative phosphorylation (OXPHOS) and glycolysis. This correlated with a higher capacity of immature αKG-moDCs to induce Th2 cells, and conventional regulatory T cells in an indolamine-dioxygenase (IDO)-1-dependent manner. Additionally, αKG increased moDCs’ capacity to induce non-conventional T regulatory (Tr)-1 and IL-10-producing CD8+T cells via up-regulated immunoglobulin-like transcript (ILT3) expression in OXPHOS-dependent manner. These results suggested that exogenous αKG-altered redox metabolism in moDCs contributed to their tolerogenic properties, which could be relevant for designing more efficient therapeutic approaches in DCs-mediated immunotherapies.",
publisher = "Ivyspring International",
journal = "International Journal of Biological Sciences, International Journal of Biological Sciences",
title = "Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response",
pages = "1087-1064",
number = "3",
volume = "20",
doi = "10.7150/ijbs.91109"
}

Milanović, M., Bekić, M., Đokić, J., Vučević, D., Čolić, M.,& Tomić, S.. (2024). Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response. in International Journal of Biological Sciences
Ivyspring International., 20(3), 1064-1087.
https://doi.org/10.7150/ijbs.91109

Milanović M, Bekić M, Đokić J, Vučević D, Čolić M, Tomić S. Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response. in International Journal of Biological Sciences. 2024;20(3):1064-1087.
doi:10.7150/ijbs.91109 .

Milanović, Marijana, Bekić, Marina, Đokić, Jelena, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, "Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response" in International Journal of Biological Sciences, 20, no. 3 (2024):1064-1087,
https://doi.org/10.7150/ijbs.91109 . .

TY  - JOUR
AU  - Drakul, Marija
AU  - Tomić, Sergej
AU  - Bekić, Marina
AU  - Mihajlović, Dušan
AU  - Vasiljević, Miloš
AU  - Rakočević, Sara
AU  - Đokić, Jelena
AU  - Popović, Nikola
AU  - Bokonjić, Dejan
AU  - Čolić, Miodrag
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/23/16829
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2220
AB  - Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Sitagliptin Induces Tolerogenic Human Dendritic Cells
IS  - 23
SP  - 16829
VL  - 24
DO  - 10.3390/ijms242316829
ER  - 

@article{
author = "Drakul, Marija and Tomić, Sergej and Bekić, Marina and Mihajlović, Dušan and Vasiljević, Miloš and Rakočević, Sara and Đokić, Jelena and Popović, Nikola and Bokonjić, Dejan and Čolić, Miodrag",
year = "2023",
abstract = "Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Sitagliptin Induces Tolerogenic Human Dendritic Cells",
number = "23",
pages = "16829",
volume = "24",
doi = "10.3390/ijms242316829"
}

Drakul, M., Tomić, S., Bekić, M., Mihajlović, D., Vasiljević, M., Rakočević, S., Đokić, J., Popović, N., Bokonjić, D.,& Čolić, M.. (2023). Sitagliptin Induces Tolerogenic Human Dendritic Cells. in International Journal of Molecular Sciences
MDPI., 24(23), 16829.
https://doi.org/10.3390/ijms242316829

Drakul M, Tomić S, Bekić M, Mihajlović D, Vasiljević M, Rakočević S, Đokić J, Popović N, Bokonjić D, Čolić M. Sitagliptin Induces Tolerogenic Human Dendritic Cells. in International Journal of Molecular Sciences. 2023;24(23):16829.
doi:10.3390/ijms242316829 .

Drakul, Marija, Tomić, Sergej, Bekić, Marina, Mihajlović, Dušan, Vasiljević, Miloš, Rakočević, Sara, Đokić, Jelena, Popović, Nikola, Bokonjić, Dejan, Čolić, Miodrag, "Sitagliptin Induces Tolerogenic Human Dendritic Cells" in International Journal of Molecular Sciences, 24, no. 23 (2023):16829,
https://doi.org/10.3390/ijms242316829 . .

TY  - JOUR
AU  - Čolić, Miodrag
AU  - Miljuš, Nataša
AU  - Đokić, Jelena
AU  - Bekić, Marina
AU  - Krivokuća, Aleksandra
AU  - Tomić, Sergej
AU  - Radojević, Dušan
AU  - Radanović, Marina
AU  - Eraković, Mile
AU  - Ismaili, Bashkim
AU  - Škrbić, Ranko
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/20/15407
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2167
AB  - Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions
IS  - 20
SP  - 15407
VL  - 24
DO  - 10.3390/ijms242015407
ER  - 

@article{
author = "Čolić, Miodrag and Miljuš, Nataša and Đokić, Jelena and Bekić, Marina and Krivokuća, Aleksandra and Tomić, Sergej and Radojević, Dušan and Radanović, Marina and Eraković, Mile and Ismaili, Bashkim and Škrbić, Ranko",
year = "2023",
abstract = "Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions",
number = "20",
pages = "15407",
volume = "24",
doi = "10.3390/ijms242015407"
}

Čolić, M., Miljuš, N., Đokić, J., Bekić, M., Krivokuća, A., Tomić, S., Radojević, D., Radanović, M., Eraković, M., Ismaili, B.,& Škrbić, R.. (2023). Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences, 24(20), 15407.
https://doi.org/10.3390/ijms242015407

Čolić M, Miljuš N, Đokić J, Bekić M, Krivokuća A, Tomić S, Radojević D, Radanović M, Eraković M, Ismaili B, Škrbić R. Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences. 2023;24(20):15407.
doi:10.3390/ijms242015407 .

Čolić, Miodrag, Miljuš, Nataša, Đokić, Jelena, Bekić, Marina, Krivokuća, Aleksandra, Tomić, Sergej, Radojević, Dušan, Radanović, Marina, Eraković, Mile, Ismaili, Bashkim, Škrbić, Ranko, "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions" in International Journal of Molecular Sciences, 24, no. 20 (2023):15407,
https://doi.org/10.3390/ijms242015407 . .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Ilić, Nataša
AU  - Đokić, Jelena
AU  - Stojanović, Dušica
AU  - Vasilev, Saša
AU  - Gruden-Movsesijan, Alisa
AU  - Tomić, Sergej
PY  - 2023
UR  - https://www.microbiota-site.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2188
AB  - ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.
C3  - 10th ISM World Congress on Targeting Microbiota
T1  - NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION
EP  - 77
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2188
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Ilić, Nataša and Đokić, Jelena and Stojanović, Dušica and Vasilev, Saša and Gruden-Movsesijan, Alisa and Tomić, Sergej",
year = "2023",
abstract = "ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.",
journal = "10th ISM World Congress on Targeting Microbiota",
title = "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2188"
}

Radojević, D., Bekić, M., Ilić, N., Đokić, J., Stojanović, D., Vasilev, S., Gruden-Movsesijan, A.,& Tomić, S.. (2023). NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota, 77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188

Radojević D, Bekić M, Ilić N, Đokić J, Stojanović D, Vasilev S, Gruden-Movsesijan A, Tomić S. NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota. 2023;:77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

Radojević, Dušan, Bekić, Marina, Ilić, Nataša, Đokić, Jelena, Stojanović, Dušica, Vasilev, Saša, Gruden-Movsesijan, Alisa, Tomić, Sergej, "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION" in 10th ISM World Congress on Targeting Microbiota (2023):77-77,
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

TY  - CONF
AU  - Bekić, Marina
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Vučević, Dragana
AU  - Vasilev, Saša
AU  - Tomić, Sergej
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2042
AB  - Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation
EP  - 97
SP  - 97
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2042
ER  - 

@conference{
author = "Bekić, Marina and Đokić, Jelena and Radojević, Dušan and Vučević, Dragana and Vasilev, Saša and Tomić, Sergej",
year = "2023",
abstract = "Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation",
pages = "97-97",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2042"
}

Bekić, M., Đokić, J., Radojević, D., Vučević, D., Vasilev, S.,& Tomić, S.. (2023). Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042

Bekić M, Đokić J, Radojević D, Vučević D, Vasilev S, Tomić S. Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference. 2023;4:97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

Bekić, Marina, Đokić, Jelena, Radojević, Dušan, Vučević, Dragana, Vasilev, Saša, Tomić, Sergej, "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation" in 4th Belgrade Bioinformatics Conference, 4 (2023):97-97,
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Vasilev, Saša
AU  - Dinić, Miroslav
AU  - Golić, Nataša
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1875
AB  - The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition
IS  - 1 (Special Edition)
SP  - 98
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1875
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Vasilev, Saša and Dinić, Miroslav and Golić, Nataša and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej and Đokić, Jelena",
year = "2021",
abstract = "The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition",
number = "1 (Special Edition)",
pages = "98",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1875"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Vasilev, S., Dinić, M., Golić, N., Vučević, D., Čolić, M., Tomić, S.,& Đokić, J.. (2021). Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 98.
https://hdl.handle.net/21.15107/rcub_imagine_1875

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Vasilev S, Dinić M, Golić N, Vučević D, Čolić M, Tomić S, Đokić J. Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica. 2021;43(1 (Special Edition)):98.
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Vasilev, Saša, Dinić, Miroslav, Golić, Nataša, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, Đokić, Jelena, "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):98,
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1613
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
EP  - 789
SP  - 776
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "789-776",
volume = "96",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - DATA
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1615
AB  - 1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium
T2  - Materials Science and Engineering C
T1  - Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1615
ER  - 

@misc{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium",
journal = "Materials Science and Engineering C",
title = "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1615"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C.
https://hdl.handle.net/21.15107/rcub_imagine_1615

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C. 2019;.
https://hdl.handle.net/21.15107/rcub_imagine_1615 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073" in Materials Science and Engineering C (2019),
https://hdl.handle.net/21.15107/rcub_imagine_1615 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1614
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
EP  - 789
SP  - 776
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "789-776",
volume = "96",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - JOUR
AU  - Marković, Milan
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Mihajlović, Dusan
AU  - Vucević, Dragana
AU  - Gazivoda, Dragan
AU  - Duka, Milos
AU  - Čolić, Miodrag
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1104
AB  - Background/Aim. Mesenchymal stem cells (MSCs) have been shown to suppress immune and inflammatory reactions. However, it is not known whether MSCs from inflammatory tissues, such as periapical lesions (PLs) have similar effects. This question was addressed in this study in which the aim was to examine the capacity of PL-MSCs for modulating cytokine production by local immune cells. Methods. PL-MSCs were isolated from asymptomatic (as) and symptomatic (sy) PLs. Their phenotype was analyzed by flow cytometry by detecting MSC surface markers. Anti-inflammatory and immunomodulatory properties of PL-MSCs were examined by measuring cytokine production in direct co-culture experiments with mononuclear cells (MNCs) isolated from asPLs and syPLs, respectively. The levels of cytokines in supernatants were determined by specific ELISA kits. Results. Both PL-MSCs lines were characterized by typical MSC phenotype, with the predominance of CD29, CD44, CD90, CD105 and CD166. However, the lines, independently of their similar phenotype had the same modulatory effect on cytokine production, but the response of asPL-MNCs and syPL-MNCs was different, in spite of similar composition of these MNCs. Both MSC lines inhibited the production of inflammatory cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-0 (TNF-0). However, IL-8 was only down-regulated in the co-culture of these MSC lines with syPL-MNCs. The PL-MSCs also modulated the production of immunoregulatory cytokines. Transforming growth factor-0 (TGF-0) was up-regulated by both as- and syPL-MNCs but IL-10 was up-regulated only by asPL-MNCs. Conclusion. Our results showed that PL-MSCs contribute to the restriction of local inflammatory and immune responses, but this effect is probably less efficient during the exacerbation of PL inflammation.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells
EP  - 480
IS  - 5
SP  - 473
VL  - 75
DO  - 10.2298/VSP160901272M
ER  - 

@article{
author = "Marković, Milan and Tomić, Sergej and Đokić, Jelena and Mihajlović, Dusan and Vucević, Dragana and Gazivoda, Dragan and Duka, Milos and Čolić, Miodrag",
year = "2018",
abstract = "Background/Aim. Mesenchymal stem cells (MSCs) have been shown to suppress immune and inflammatory reactions. However, it is not known whether MSCs from inflammatory tissues, such as periapical lesions (PLs) have similar effects. This question was addressed in this study in which the aim was to examine the capacity of PL-MSCs for modulating cytokine production by local immune cells. Methods. PL-MSCs were isolated from asymptomatic (as) and symptomatic (sy) PLs. Their phenotype was analyzed by flow cytometry by detecting MSC surface markers. Anti-inflammatory and immunomodulatory properties of PL-MSCs were examined by measuring cytokine production in direct co-culture experiments with mononuclear cells (MNCs) isolated from asPLs and syPLs, respectively. The levels of cytokines in supernatants were determined by specific ELISA kits. Results. Both PL-MSCs lines were characterized by typical MSC phenotype, with the predominance of CD29, CD44, CD90, CD105 and CD166. However, the lines, independently of their similar phenotype had the same modulatory effect on cytokine production, but the response of asPL-MNCs and syPL-MNCs was different, in spite of similar composition of these MNCs. Both MSC lines inhibited the production of inflammatory cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-0 (TNF-0). However, IL-8 was only down-regulated in the co-culture of these MSC lines with syPL-MNCs. The PL-MSCs also modulated the production of immunoregulatory cytokines. Transforming growth factor-0 (TGF-0) was up-regulated by both as- and syPL-MNCs but IL-10 was up-regulated only by asPL-MNCs. Conclusion. Our results showed that PL-MSCs contribute to the restriction of local inflammatory and immune responses, but this effect is probably less efficient during the exacerbation of PL inflammation.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells",
pages = "480-473",
number = "5",
volume = "75",
doi = "10.2298/VSP160901272M"
}

Marković, M., Tomić, S., Đokić, J., Mihajlović, D., Vucević, D., Gazivoda, D., Duka, M.,& Čolić, M.. (2018). Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 75(5), 473-480.
https://doi.org/10.2298/VSP160901272M

Marković M, Tomić S, Đokić J, Mihajlović D, Vucević D, Gazivoda D, Duka M, Čolić M. Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells. in Vojnosanitetski pregled. 2018;75(5):473-480.
doi:10.2298/VSP160901272M .

Marković, Milan, Tomić, Sergej, Đokić, Jelena, Mihajlović, Dusan, Vucević, Dragana, Gazivoda, Dragan, Duka, Milos, Čolić, Miodrag, "Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells" in Vojnosanitetski pregled, 75, no. 5 (2018):473-480,
https://doi.org/10.2298/VSP160901272M . .

TY  - JOUR
AU  - Pavlović, Bojan
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Vasilijić, Sasa
AU  - Vucević, Dragana
AU  - Lukić, Jovanka
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Marković, Milan
AU  - Čolić, Miodrag
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/846
AB  - Background aims. Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. Methods. We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. Results. Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD 14, low expression of CD la and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1 beta and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-beta production by fDC-primed CD3(+)T cells and their stronger antiproliferative capacity. Conclusions. We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.
PB  - Elsevier Sci Ltd, Oxford
T2  - Cytotherapy
T1  - Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties
EP  - 1776
IS  - 12
SP  - 1763
VL  - 17
DO  - 10.1016/j.jcyt.2015.08.001
ER  - 

@article{
author = "Pavlović, Bojan and Tomić, Sergej and Đokić, Jelena and Vasilijić, Sasa and Vucević, Dragana and Lukić, Jovanka and Gruden-Movsesijan, Alisa and Ilić, Nataša and Marković, Milan and Čolić, Miodrag",
year = "2015",
abstract = "Background aims. Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. Methods. We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. Results. Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD 14, low expression of CD la and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1 beta and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-beta production by fDC-primed CD3(+)T cells and their stronger antiproliferative capacity. Conclusions. We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Cytotherapy",
title = "Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties",
pages = "1776-1763",
number = "12",
volume = "17",
doi = "10.1016/j.jcyt.2015.08.001"
}

Pavlović, B., Tomić, S., Đokić, J., Vasilijić, S., Vucević, D., Lukić, J., Gruden-Movsesijan, A., Ilić, N., Marković, M.,& Čolić, M.. (2015). Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties. in Cytotherapy
Elsevier Sci Ltd, Oxford., 17(12), 1763-1776.
https://doi.org/10.1016/j.jcyt.2015.08.001

Pavlović B, Tomić S, Đokić J, Vasilijić S, Vucević D, Lukić J, Gruden-Movsesijan A, Ilić N, Marković M, Čolić M. Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties. in Cytotherapy. 2015;17(12):1763-1776.
doi:10.1016/j.jcyt.2015.08.001 .

Pavlović, Bojan, Tomić, Sergej, Đokić, Jelena, Vasilijić, Sasa, Vucević, Dragana, Lukić, Jovanka, Gruden-Movsesijan, Alisa, Ilić, Nataša, Marković, Milan, Čolić, Miodrag, "Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties" in Cytotherapy, 17, no. 12 (2015):1763-1776,
https://doi.org/10.1016/j.jcyt.2015.08.001 . .

TY  - JOUR
AU  - Đokić, Jelena
AU  - Tomić, Sergej
AU  - Marković, Milan
AU  - Milosavljević, Petar
AU  - Čolić, Miodrag
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/701
AB  - Immunoregulatory mechanisms within periapical lesions (PLs) are as of yet unexplored. Considering the crucial role of DCs in controlling the immune response within PLs, the immunomodulatory properties of mesenchymal stem cells (MSCs), and the colocalization of MSCs and DCs in situ, we wondered whether MSCs from PLs modulate the development and functions of DCs. Using a model of monocyte-derived DCs, we showed that PL-MSCs inhibited differentiation of DCs via soluble factors, of which IL-6 had a minor effect, but did not impair their subsequent maturation induced by pro-inflammatory cytokines. However, upon maturation such DCs favored the production of Th2/Th17 cytokines by allogenic CD4(+) lymphocytes in coculture, compared with mature DCs differentiated without PL-MSCs. PL-MSC-differentiated DCs, cultivated with pro-inflammatory cytokines and PL-MSCs, although phenotypically mature, exhibited poor allostimulatory activity, induced anergy, Th2 polarization, differentiation of suppressive CD4(+)CD25(high)CD39(+) Treg-cell subsets via IDO-1-, ILT-3-, and ILT-4-dependent mechanisms, and increased production of TGF- in the coculture. In contrast, DCs cultivated with PL-MSCs only during maturation stimulated proliferation and Th1 polarization of CD4(+) T cells in an IL-12-independent manner. In conclusion, PL-MSCs significantly modulate the development and functions of DCs, depending on the phase of DCs development during which the interaction occurs.
PB  - Wiley-Blackwell, Hoboken
T2  - European Journal of Immunology
T1  - Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells
EP  - 1872
IS  - 7
SP  - 1862
VL  - 43
DO  - 10.1002/eji.201243010
ER  - 

@article{
author = "Đokić, Jelena and Tomić, Sergej and Marković, Milan and Milosavljević, Petar and Čolić, Miodrag",
year = "2013",
abstract = "Immunoregulatory mechanisms within periapical lesions (PLs) are as of yet unexplored. Considering the crucial role of DCs in controlling the immune response within PLs, the immunomodulatory properties of mesenchymal stem cells (MSCs), and the colocalization of MSCs and DCs in situ, we wondered whether MSCs from PLs modulate the development and functions of DCs. Using a model of monocyte-derived DCs, we showed that PL-MSCs inhibited differentiation of DCs via soluble factors, of which IL-6 had a minor effect, but did not impair their subsequent maturation induced by pro-inflammatory cytokines. However, upon maturation such DCs favored the production of Th2/Th17 cytokines by allogenic CD4(+) lymphocytes in coculture, compared with mature DCs differentiated without PL-MSCs. PL-MSC-differentiated DCs, cultivated with pro-inflammatory cytokines and PL-MSCs, although phenotypically mature, exhibited poor allostimulatory activity, induced anergy, Th2 polarization, differentiation of suppressive CD4(+)CD25(high)CD39(+) Treg-cell subsets via IDO-1-, ILT-3-, and ILT-4-dependent mechanisms, and increased production of TGF- in the coculture. In contrast, DCs cultivated with PL-MSCs only during maturation stimulated proliferation and Th1 polarization of CD4(+) T cells in an IL-12-independent manner. In conclusion, PL-MSCs significantly modulate the development and functions of DCs, depending on the phase of DCs development during which the interaction occurs.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "European Journal of Immunology",
title = "Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells",
pages = "1872-1862",
number = "7",
volume = "43",
doi = "10.1002/eji.201243010"
}

Đokić, J., Tomić, S., Marković, M., Milosavljević, P.,& Čolić, M.. (2013). Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells. in European Journal of Immunology
Wiley-Blackwell, Hoboken., 43(7), 1862-1872.
https://doi.org/10.1002/eji.201243010

Đokić J, Tomić S, Marković M, Milosavljević P, Čolić M. Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells. in European Journal of Immunology. 2013;43(7):1862-1872.
doi:10.1002/eji.201243010 .

Đokić, Jelena, Tomić, Sergej, Marković, Milan, Milosavljević, Petar, Čolić, Miodrag, "Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells" in European Journal of Immunology, 43, no. 7 (2013):1862-1872,
https://doi.org/10.1002/eji.201243010 . .

TY  - JOUR
AU  - Đokić, Jelena
AU  - Rudolf, Rebeka
AU  - Tomić, Sergej
AU  - Stopić, Srecko
AU  - Friedrich, Bernd
AU  - Budić, Bojan
AU  - Anzel, Ivan
AU  - Čolić, Miodrag
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/559
AB  - We prepared 5 different fractions of nanoparticles from the gold scrap, by using a new technology, Ultrasonic Spray Pirolysis (USP). The aim of this study was to characterize the microstructure and cytotoxicity of the nanoparticles along with their immunomodulatory properties, using Concanavaline A (ConA)-treated rat splenocytes as a model of activated immune cells. Fractions 1 and 2, composed of pure gold nanoparticles, although non-cytotoxic, reduced cellular proliferation. Fraction 2, containing particles smaller in size and lesser agglomerated than fraction 1, up- and down-regulated the production of IL-2 and IL-10, respectively, by activated splenocytes. Fraction 3, containing nanoparticles composed of Au and up to 3 at.% Cu, was non-cytotoxic, but reduced IL-2 production and cell proliferation. Fractions 4 and 5, contaminated with alloying elements from the gold scrap, were cytotoxic. The extent of cytotoxicity and subsequent reduction of cytokine production, as well as the mode of cell death, depended on their composition. In conclusion, we showed that USP enables the synthesis of gold nanoparticles, which could be suitable for various biological applications, and that ConA-treated splenocytes represent a reliable model for fast and accurate evaluation of the immunotoxicological profiles of these particles. However, it is necessary to improve this technology and investigate further some of the immunomodulatory mechanisms using more specific immunological tests.
PB  - Amer Scientific Publishers, Valencia
T2  - Journal of Biomedical Nanotechnology
T1  - Immunomodulatory Properties of Nanoparticles Obtained by Ultrasonic Spray Pirolysis from Gold Scrap
EP  - 538
IS  - 3
SP  - 528
VL  - 8
DO  - 10.1166/jbn.2012.1405
ER  - 

@article{
author = "Đokić, Jelena and Rudolf, Rebeka and Tomić, Sergej and Stopić, Srecko and Friedrich, Bernd and Budić, Bojan and Anzel, Ivan and Čolić, Miodrag",
year = "2012",
abstract = "We prepared 5 different fractions of nanoparticles from the gold scrap, by using a new technology, Ultrasonic Spray Pirolysis (USP). The aim of this study was to characterize the microstructure and cytotoxicity of the nanoparticles along with their immunomodulatory properties, using Concanavaline A (ConA)-treated rat splenocytes as a model of activated immune cells. Fractions 1 and 2, composed of pure gold nanoparticles, although non-cytotoxic, reduced cellular proliferation. Fraction 2, containing particles smaller in size and lesser agglomerated than fraction 1, up- and down-regulated the production of IL-2 and IL-10, respectively, by activated splenocytes. Fraction 3, containing nanoparticles composed of Au and up to 3 at.% Cu, was non-cytotoxic, but reduced IL-2 production and cell proliferation. Fractions 4 and 5, contaminated with alloying elements from the gold scrap, were cytotoxic. The extent of cytotoxicity and subsequent reduction of cytokine production, as well as the mode of cell death, depended on their composition. In conclusion, we showed that USP enables the synthesis of gold nanoparticles, which could be suitable for various biological applications, and that ConA-treated splenocytes represent a reliable model for fast and accurate evaluation of the immunotoxicological profiles of these particles. However, it is necessary to improve this technology and investigate further some of the immunomodulatory mechanisms using more specific immunological tests.",
publisher = "Amer Scientific Publishers, Valencia",
journal = "Journal of Biomedical Nanotechnology",
title = "Immunomodulatory Properties of Nanoparticles Obtained by Ultrasonic Spray Pirolysis from Gold Scrap",
pages = "538-528",
number = "3",
volume = "8",
doi = "10.1166/jbn.2012.1405"
}

Đokić, J., Rudolf, R., Tomić, S., Stopić, S., Friedrich, B., Budić, B., Anzel, I.,& Čolić, M.. (2012). Immunomodulatory Properties of Nanoparticles Obtained by Ultrasonic Spray Pirolysis from Gold Scrap. in Journal of Biomedical Nanotechnology
Amer Scientific Publishers, Valencia., 8(3), 528-538.
https://doi.org/10.1166/jbn.2012.1405

Đokić J, Rudolf R, Tomić S, Stopić S, Friedrich B, Budić B, Anzel I, Čolić M. Immunomodulatory Properties of Nanoparticles Obtained by Ultrasonic Spray Pirolysis from Gold Scrap. in Journal of Biomedical Nanotechnology. 2012;8(3):528-538.
doi:10.1166/jbn.2012.1405 .

Đokić, Jelena, Rudolf, Rebeka, Tomić, Sergej, Stopić, Srecko, Friedrich, Bernd, Budić, Bojan, Anzel, Ivan, Čolić, Miodrag, "Immunomodulatory Properties of Nanoparticles Obtained by Ultrasonic Spray Pirolysis from Gold Scrap" in Journal of Biomedical Nanotechnology, 8, no. 3 (2012):528-538,
https://doi.org/10.1166/jbn.2012.1405 . .

TY  - JOUR
AU  - Rajković, Ivan
AU  - Dragicević, Ana
AU  - Vasilijić, Sasa
AU  - Bozić, Biljana
AU  - Dzopalić, Tanja
AU  - Tomić, Sergej
AU  - Majstorović, Ivana
AU  - Vucević, Dragana
AU  - Đokić, Jelena
AU  - Balint, Bela
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/477
AB  - P gt Langerhans' cells (LCs) represent a specific subset of dendritic cells (DCs) which are important for detecting and processing pathogens that penetrate the skin and epithelial barriers. The aim of our study was to explain what makes their in vitro counterparts - monocyte-derived Langerhans'-like cells (MoLCs) - unique compared with monocyte-derived dendritic cells (MoDCs). Immature MoDCs were generated by incubating peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. The addition of transforming growth factor-beta (TGF-beta) to this cytokine cocktail resulted in the generation of MoLCs. MoLCs showed a lower expression of CD83, CD86, HLA-DR and CCR7 compared with MoDCs, regardless of their maturational status. Both immature and mature MoLCs secreted higher quantities of IL-23 compared with MoDCs and this finding correlated with a higher secretion of IL-17 in co-culture of MoLCs with allogeneic CD4(+) T cells. Mature MoLCs, which produced higher levels of IL-12 and lower levels of IL-10 compared with mature MoDCs, were more potent at inducing interferon-gamma (IFN-gamma) production by CD4(+) T cells in the co-culture system. In conclusion, the finding that mature MoLCs stimulate stronger T-helper 1 and T-helper 17 immune responses than mature MoDCs, makes them better candidates for use in the preparation of anti-tumour DC vaccines.
PB  - Wiley, Hoboken
T2  - Immunology
T1  - Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells
EP  - 225
IS  - 2
SP  - 217
VL  - 132
DO  - 10.1111/j.1365-2567.2010.03356.x
ER  - 

@article{
author = "Rajković, Ivan and Dragicević, Ana and Vasilijić, Sasa and Bozić, Biljana and Dzopalić, Tanja and Tomić, Sergej and Majstorović, Ivana and Vucević, Dragana and Đokić, Jelena and Balint, Bela and Čolić, Miodrag",
year = "2011",
abstract = "P gt Langerhans' cells (LCs) represent a specific subset of dendritic cells (DCs) which are important for detecting and processing pathogens that penetrate the skin and epithelial barriers. The aim of our study was to explain what makes their in vitro counterparts - monocyte-derived Langerhans'-like cells (MoLCs) - unique compared with monocyte-derived dendritic cells (MoDCs). Immature MoDCs were generated by incubating peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. The addition of transforming growth factor-beta (TGF-beta) to this cytokine cocktail resulted in the generation of MoLCs. MoLCs showed a lower expression of CD83, CD86, HLA-DR and CCR7 compared with MoDCs, regardless of their maturational status. Both immature and mature MoLCs secreted higher quantities of IL-23 compared with MoDCs and this finding correlated with a higher secretion of IL-17 in co-culture of MoLCs with allogeneic CD4(+) T cells. Mature MoLCs, which produced higher levels of IL-12 and lower levels of IL-10 compared with mature MoDCs, were more potent at inducing interferon-gamma (IFN-gamma) production by CD4(+) T cells in the co-culture system. In conclusion, the finding that mature MoLCs stimulate stronger T-helper 1 and T-helper 17 immune responses than mature MoDCs, makes them better candidates for use in the preparation of anti-tumour DC vaccines.",
publisher = "Wiley, Hoboken",
journal = "Immunology",
title = "Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells",
pages = "225-217",
number = "2",
volume = "132",
doi = "10.1111/j.1365-2567.2010.03356.x"
}

Rajković, I., Dragicević, A., Vasilijić, S., Bozić, B., Dzopalić, T., Tomić, S., Majstorović, I., Vucević, D., Đokić, J., Balint, B.,& Čolić, M.. (2011). Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells. in Immunology
Wiley, Hoboken., 132(2), 217-225.
https://doi.org/10.1111/j.1365-2567.2010.03356.x

Rajković I, Dragicević A, Vasilijić S, Bozić B, Dzopalić T, Tomić S, Majstorović I, Vucević D, Đokić J, Balint B, Čolić M. Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells. in Immunology. 2011;132(2):217-225.
doi:10.1111/j.1365-2567.2010.03356.x .

Rajković, Ivan, Dragicević, Ana, Vasilijić, Sasa, Bozić, Biljana, Dzopalić, Tanja, Tomić, Sergej, Majstorović, Ivana, Vucević, Dragana, Đokić, Jelena, Balint, Bela, Čolić, Miodrag, "Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells" in Immunology, 132, no. 2 (2011):217-225,
https://doi.org/10.1111/j.1365-2567.2010.03356.x . .

TY  - JOUR
AU  - Dzopalić, Tanja
AU  - Vucević, Dragana
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Chinou, Ioanna
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/482
AB  - Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4(+)T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-gamma in co-culture with allogeneic CD4(+)T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses.
PB  - Elsevier Sci Ltd, Oxford
T2  - Food Chemistry
T1  - 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells
EP  - 1217
IS  - 3
SP  - 1211
VL  - 126
DO  - 10.1016/j.foodchem.2010.12.004
ER  - 

@article{
author = "Dzopalić, Tanja and Vucević, Dragana and Tomić, Sergej and Đokić, Jelena and Chinou, Ioanna and Čolić, Miodrag",
year = "2011",
abstract = "Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4(+)T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-gamma in co-culture with allogeneic CD4(+)T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Food Chemistry",
title = "3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells",
pages = "1217-1211",
number = "3",
volume = "126",
doi = "10.1016/j.foodchem.2010.12.004"
}

Dzopalić, T., Vucević, D., Tomić, S., Đokić, J., Chinou, I.,& Čolić, M.. (2011). 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells. in Food Chemistry
Elsevier Sci Ltd, Oxford., 126(3), 1211-1217.
https://doi.org/10.1016/j.foodchem.2010.12.004

Dzopalić T, Vucević D, Tomić S, Đokić J, Chinou I, Čolić M. 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells. in Food Chemistry. 2011;126(3):1211-1217.
doi:10.1016/j.foodchem.2010.12.004 .

Dzopalić, Tanja, Vucević, Dragana, Tomić, Sergej, Đokić, Jelena, Chinou, Ioanna, Čolić, Miodrag, "3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells" in Food Chemistry, 126, no. 3 (2011):1211-1217,
https://doi.org/10.1016/j.foodchem.2010.12.004 . .

TY  - JOUR
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Vasilijić, Sasa
AU  - Vucević, Dragana
AU  - Todorović, Vera
AU  - Supić, Gordana
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/529
AB  - Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-beta and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-beta antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-beta and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-beta production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-beta production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Stem Cells and Development
T1  - Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists
EP  - 708
IS  - 4
SP  - 695
VL  - 20
DO  - 10.1089/scd.2010.0145
ER  - 

@article{
author = "Tomić, Sergej and Đokić, Jelena and Vasilijić, Sasa and Vucević, Dragana and Todorović, Vera and Supić, Gordana and Čolić, Miodrag",
year = "2011",
abstract = "Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-beta and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-beta antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-beta and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-beta production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-beta production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Stem Cells and Development",
title = "Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists",
pages = "708-695",
number = "4",
volume = "20",
doi = "10.1089/scd.2010.0145"
}

Tomić, S., Đokić, J., Vasilijić, S., Vucević, D., Todorović, V., Supić, G.,& Čolić, M.. (2011). Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists. in Stem Cells and Development
Mary Ann Liebert, Inc, New Rochelle., 20(4), 695-708.
https://doi.org/10.1089/scd.2010.0145

Tomić S, Đokić J, Vasilijić S, Vucević D, Todorović V, Supić G, Čolić M. Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists. in Stem Cells and Development. 2011;20(4):695-708.
doi:10.1089/scd.2010.0145 .

Tomić, Sergej, Đokić, Jelena, Vasilijić, Sasa, Vucević, Dragana, Todorović, Vera, Supić, Gordana, Čolić, Miodrag, "Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists" in Stem Cells and Development, 20, no. 4 (2011):695-708,
https://doi.org/10.1089/scd.2010.0145 . .