Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism

Chen, Ke; Wang, Ding; Du, Wei; Han, Zhibo; Ren, He; Cheng, Ying; Yang, Shangda; Zhu, Delin; Bayard, Françis; Han, Zhong Chao

doi:10.1016/j.clim.2010.01.015

Cited by 182 publications

(168 citation statements)

References 48 publications

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“…Under inflammatory conditions of the environment, PGE2 is induced, substantially increasing secreted amounts from MSCs. LPS as well as cytokines like IFNγ, TNFα, IL-1β are mediators directly regulating PGE2 production from MSCs [227,229,230] . Multiple studies show that direct contact of PBMCs, monocytes and NK cells with MSCs induces PGE2 augmentation via the mentioned cytokines [44,[227][228][229] .…”

Section: Prostaglandin E2mentioning

confidence: 99%

“…LPS as well as cytokines like IFNγ, TNFα, IL-1β are mediators directly regulating PGE2 production from MSCs [227,229,230] . Multiple studies show that direct contact of PBMCs, monocytes and NK cells with MSCs induces PGE2 augmentation via the mentioned cytokines [44,[227][228][229] . Activated by environmental signals, PGE2 from MSCs exert regulatory influence on the activation status, proliferation, differentiation and function of immune cells from adaptive and innate immunity.…”

Section: Prostaglandin E2mentioning

confidence: 99%

“…Activated by environmental signals, PGE2 from MSCs exert regulatory influence on the activation status, proliferation, differentiation and function of immune cells from adaptive and innate immunity. Acting by a contact or paracrine manner [229,231] , PGE2 has a systemic antiinflammatory effect of reducing TNFα, IL-6 and vascular permeability in an experimental model of sepsis [230] . Particularly, the cellular targets of PGE2 are PBMCs, NK cells, monocytes, macrophages and the transitional processes of differentiation of monocytes into immature DCs [228,230,232] .…”

Section: Prostaglandin E2mentioning

confidence: 99%

“…Particularly, the cellular targets of PGE2 are PBMCs, NK cells, monocytes, macrophages and the transitional processes of differentiation of monocytes into immature DCs [228,230,232] . PGE2 indirectly affects polyclonally or allogenically activated PBMCs by substantial suppression of proliferation and IFNγ secretion [227,229,231] . Simultaneously, the effect on T cells is accompanied by a prevailing bias towards IL-4 production [227] and induction of regulatory IL-10 secreting T cells [183,233] .…”

Section: Prostaglandin E2mentioning

confidence: 99%

See 3 more Smart Citations

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

526

392

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According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system. © 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Mesenchymal stem cells; Immunomodulation; Cytokines; Chemokines; Dendritic cells Core tip: Autoimmune diseases affect approximately 5% of the human population, leading to serious disability and effective methods to treat these diseases are still not perfect. Mesenchymal stem cells (MSCs) are assumed to be promising agents, both for regenerative medicine and cell therapy for autoimmune disorders. Under the influence of some factors, mesenchymal stem cells secrete cytokines which induce suppression of the immune response. Studies on the secreted cytokines and the precise mechanisms involved in these suppressive mechanisms would create possibilities for efficient application of MSCs as a therapeutic means for treatment of autoimmune diseases.Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, REVIEWSubmit a

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Section: Prostaglandin E2mentioning

confidence: 99%

Section: Prostaglandin E2mentioning

confidence: 99%

Section: Prostaglandin E2mentioning

confidence: 99%

Section: Prostaglandin E2mentioning

confidence: 99%

See 2 more Smart Citations

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

526

392

View full text Add to dashboard Cite

show abstract

“…In human MSC, the reported pathways of immune suppression by MSC include the indoleamine 2,3-deoxygenase (IDO) [21,22], cyclooxygenase [23][24][25], TGF-b [26], soluble IL-1Ra [27,28], soluble MHC [29,30], and the PD-L1 pathways [31,32]. In general however, the IDO-dependent pathway is considered the primary mechanism of human MSC suppression of activated immune effector cells [21].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-b signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-b and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-b pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

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Potential surrogate quantitative immunomodulatory potency assay for monitoring human umbilical cord‐derived mesenchymal stem cells production

Teng

Sung

Wen

et al. 2021

Cell Biology International

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Mesenchymal stem cells (MSCs) play an important role as immune modulator through interaction with several immune cells, including macrophages. In this study, the immunomodulatory potency of human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) was demonstrated in the in vivo middle cerebral artery occlusion (MCAo)‐induced brain injury rat model and in vitro THP‐1‐derived macrophages model. At 24 h after induction of MCAo, hUC‐MSCs was administered via tail vein as a single dose. Remarkably, hUC‐MSCs could inhibit M1 polarization and promote M2 polarization of microglia in vivo after 14 days induction of MCAo. Compared with THP‐1‐derived macrophages which had been stimulated by lipopolysaccharide, the secretion of proinflammatory cytokines, tumor necrosis factor‐α (TNF‐α) and interferon‐γ inducible protein (IP‐10), were significantly reduced in the presence of hUC‐MSCs. Moreover, the secretion of anti‐inflammatory cytokine, interleukin‐10 (IL‐10), was significantly increased after cocultured with hUC‐MSCs. Prostaglandins E2 (PGE2), secreted by hUC‐MSCs, is one of the crucial immunomodulatory factors and could be inhibited in the presence of COX2 inhibitor, NS‐398. PGE2 inhibition suppressed hUC‐MSCs immunomodulatory capability, which was restored after addition of synthetic PGE2, establishing the minimum amount of PGE2 required for immunomodulation. In conclusion, our data suggested that PGE2 is a crucial potency marker involved in the therapeutic activity of hUC‐MSCs through macrophages immune response modulation and cytokines regulation. This study provides the model for the development of a surrogate quantitative potency assay of immunomodulation in stem cells production.

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Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism

Cited by 182 publications

References 48 publications

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

Potential surrogate quantitative immunomodulatory potency assay for monitoring human umbilical cord‐derived mesenchymal stem cells production

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