Characterization and immunosuppressive properties of mesenchymal stem cells from periapical lesions

Đokić, Jelena; Tomić, Sergej; Cerović, Snežana; Todorovic, Vesna; Rudolf, Rebeka; Čolić, Miodrag

doi:10.1111/j.1600-051x.2012.01917.x

Cited by 40 publications

(47 citation statements)

References 55 publications

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“…We have previously described in details morphological, phenotypical and differentiation characteristics of PL-MSCs isolated from three different donors (12). In this work we used one of the lines to study its immunoregulatory properties.…”

Section: Resultsmentioning

confidence: 99%

“…We found that STRO-1, a marker for MSCs (15), showed a lower membrane expression. However, this marker including CD46, was localized predominately intracellularly, as demonstrated by immunochystochemistry (12).…”

Section: Discussionmentioning

confidence: 99%

“…The detailed protocol for the isolation of MSCs has been described in our previous paper (12). Briefly, PLs tissues were digested in a Dulbecco's modified Eagle's medium (DMEM; Sigma, Munich, Germany) solution with a type I collagenase (1mg/mL; Sigma) and DNAase (25 mg/mL; Sigma) for 1 hr in an incubator.…”

Section: Isolation and Cultivation Of Cellsmentioning

confidence: 99%

“…The flow cytometry was used for characterization of a clone after the fourth passage, as previously described (12,13) leukocyte antigen (HLA)-DR-phycoerithryne (PE), and mouse IgG1a negative control-PE were also from Serotec. The indirect labelling was performed using anti-STRO-1 (Millipore/Chemicon) mAb followed by secondary anti-mouse IgG1-FITC mAb.…”

Section: Phenotypic Characterization Of Pl-mscsmentioning

confidence: 99%

“…The inflamed dental tissue could also be a source of MSCs, but only a few papers have described the presence of MSCs at the site of an inflamed periodontal ligament or dental papilla (10, 11). We have recently isolated MSCs from PLs and found their significant anti-proliferative and immunomodulatory effects on lymphocytes in culture, and the ability to suppress the production of proinflammatory cytokines by inflammatory cells (ICs) isolated from PLs (PL-ICs) (12). In this work we studied the effect of PL-MSCs on the production of immunoregulatory cytokines by PL-ICs in vitro, using either direct or indirect co-culture assays.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture / Mezenhimske matične ćelije iz periapeksnih lezija stimulišu produkciju imunoregulacijskih citokina od strane inflamacijskih ćelija u kulturi

Marković¹,

Tomić²,

Djokić³

et al. 2015

Acta Facultatis Medicae Naissensis

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The pathophysiology of periapical lesions (PLs) is under control of pro-inflammatory and anti-inflammatory (mainly immunoregulatory) cytokines. We have recently established mesenchymal stem cells (MSCs) from PLs and showed their suppressive effects on the production of proinflammatory cytokines from PLs inflammatory cells (ICs). In this work we studied the production of interleukin (IL)-10, IL-27 and transforming growth factor (TGF)-β, by PL-ICs in direct or indirect contacts with PL-MSCs. PL-ICs, which were isolated from four different asymptomatic PLs, predominantly composed of lymphocytes, followed by neutrophil granulocytes, macrophages and plasma cells. PLMSCs, expressing typical MSC markers, were co-cultivated with PL-ICs at 1:10 ratio, either in direct contact or in a transwell-system, for 24 hours. The levels of cytokines in cell-culture supernatants were tested by ELISA. The results showed that PL-MSCs up-regulated the production of all three immunoregulatory cytokines by PL-ICs. PL-MSCs stimulated the production of IL-10 and IL-27 via soluble factors, whereas the up-regulation of TGF-β required direct cell-to-cell contacts. In conclusion, our results showed for the first time the involvement of PL-MSCs in restriction of inflammation in PLs by up-regulation of immunoregulatory cytokines.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Isolation and Cultivation Of Cellsmentioning

confidence: 99%

Section: Phenotypic Characterization Of Pl-mscsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture / Mezenhimske matične ćelije iz periapeksnih lezija stimulišu produkciju imunoregulacijskih citokina od strane inflamacijskih ćelija u kulturi

Marković¹,

Tomić²,

Djokić³

et al. 2015

Acta Facultatis Medicae Naissensis

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In vitro evaluation of periapical lesion‐derived stem cells for dental pulp tissue engineering

Mao

et al. 2021

FEBS Open Bio

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Dental pulp tissue engineering is a promising alternative treatment for pulpitis and periapical periodontitis, and dental pulp stem cells (DPSCs) are considered to be the gold standard for dental seed cell research. Periapical lesions harbor mesenchymal stem cells with the capacity for self‐renewal and multilineage differentiation. However, it remains unknown whether these periapical lesion‐derived stem cells (PLDSCs) are suitable for dental pulp tissue engineering. To investigate this possibility, PLDSCs and DPSCs were isolated using the tissue outgrowth method and cultured under identical conditions. We then performed in vitro experiments to investigate their biological characteristics. Our results indicate that PLDSCs proliferate actively in vitro and exhibit similar morphology, immunophenotype and multilineage differentiation ability as DPSCs. Simultaneously, PLDSCs exhibit stronger migrative ability and express more vascular endothelial growth factor and glial cell line‐derived neurotrophic factor than DPSCs, and PLDSC‐derived conditioned medium was more effective in tube formation assay. The mRNA expression levels of immunomodulatory genes HLA‐G , IDO and ICAM‐1 were also higher in PLDSCs. However, regarding osteo/odontogenic differentiation, PLDSCs showed weaker alkaline phosphatase staining and lower calcified nodule formation compared to DPSCs, as well as lower expression of ALP , RUNX2 and DSPP , as confirmed by a quantitative RT‐PCR. The osteo/odontogenic protein expression levels of DSPP, RUNX2, DMP1 and SP7 were also higher in DPSCs. The present study demonstrates that PLDSCs demonstrate potential use as seed cells for dental pulp regeneration, especially for achieving enhanced neurovascularization.

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Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

et al. 2013

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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-β 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. Keywords: Dendritic cells r Mesenchymal stem cells r Periapical lesions r Th polarizationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPeriapical lesions (PLs) are a common pathology within the human population initiated by the bacterial invasion of the root canal and develop from an acute inflammatory response to the formation of granulomas or cysts infiltrated by various inflammatory cells [1].Correspondence: Prof. MiodragČolić e-mail: fakultet.vma@mod.gov.rs Furthermore, cytokines produced by Th cells have been shown to play a crucial role in PLs pathogenesis. Namely, Th1-and Th17-derived cytokines promote inflammation, bone resorption, and disease progression. Th2 cells seem to be important for the later phases of PLs development, whereas IL-10 and TGF-β produced by Treg cells seem to be important for the healing processes within PLs [2,3]. However, it is not yet clear which mediators and cells are involved crucially in the regulation of Th-cell commitment during the development, maintenance, and resolution of the disease.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 1862-1872 Immunomodulation 1863DCs are the key regulatory and decision-making cells with a unique ability to activate naive T cells and polarize their development. These cells can be differentiated in vitro from monocytes or CD34 + -progenitors with GM-CSF and IL-4, generating CD1a + CD14 − immature DCs (iDCs) [4]. Alternatively, in the absence of IL-4, GM-CSF induces the differ...

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Characterization and immunosuppressive properties of mesenchymal stem cells from periapical lesions

Abstract: The differentiation potential of PL-MSCs and their immunosuppressive/anti-inflammatory properties could be beneficial for the treatment of chronic periodontal diseases.

Cited by 40 publications

References 55 publications

Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture / Mezenhimske matične ćelije iz periapeksnih lezija stimulišu produkciju imunoregulacijskih citokina od strane inflamacijskih ćelija u kulturi

Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture / Mezenhimske matične ćelije iz periapeksnih lezija stimulišu produkciju imunoregulacijskih citokina od strane inflamacijskih ćelija u kulturi

In vitro evaluation of periapical lesion‐derived stem cells for dental pulp tissue engineering

Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte‐derived dendritic cells

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