Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells

Ivanova‐Todorova, Ekaterina; Bochev, Ivan; Mourdjeva, Milena; Dimitrov, Rumen; Bukarev, Dimitar; Kyurkchiev, Stanimir; Tivchev, Petar; Altŭnkova, I; Kyurkchiev, Dobroslav

doi:10.1016/j.imlet.2009.07.010

Cited by 196 publications

(141 citation statements)

References 41 publications

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“…Most authors report either a lack of differences or find some quantitative differences in the levels of cytokines secreted by AT-MSCs or BM-MSCs [58][59][60] . Our experimental data also show some quantitative differences in the cytokine secretion [37] . Similar findings are reported when embryonic, fetal and adult MSCs have been compared [61] .…”

Section: Introductionsupporting

confidence: 61%

“…MSCs can also influence T-cell responses indirectly through suppression of CD34+ progenitor cell and monocyte-derived dendritic cell differentiation, as well as through inhibition of their antigen-presenting functions [37][38][39][40] . A number of studies have demonstrated that MSCs have the capacity to inhibit B-cell proliferation, differentiation and immunoglobulin production in vitro [41,42] as well as to down-regulate the proliferation, cytokine production and cytotoxicity of NK cells [43,44] .…”

Section: Introductionmentioning

confidence: 99%

“…Although there is no definite opinion about the conditions under which MSCs secrete IL-10, their role is indisputable as a factor which causes indirect stimulation of IL-10 secretion by other cells. It has been shown that MSCs secrete factors which up-regulate the secretion of IL-10 by peripheral blood mononuclear cells (PBMCs) [59] , as well as by tolerogenic macrophages [89] and tolerogenic DCs [37,69,90] . It is also assumed although not undoubtedly proven that MSCs induce generation of Tregs [59,62,90] and our results show that when cultured in MSC conditioned medium, the fraction of CD4+FoxP3+ lymphocytes is increased and this effect is directly induced by MSCs without any involvement of DCs [69] .…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

526

392

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“…Further, ADSC's immunosuppressive activity appears to be mediated through an interleukin-6 (IL-6)-dependent inhibition of dendritic cell differentiation and downregulation of MHC-II, CD40, and CD86 on mature dendritic cells [38]. A subsequent study further showed that ADSC was more potent than BMSC in suppressing dendritic cell differentiation and downregulation of costimulatory molecules on the surface of dendritic cells [43].…”

Section: Evidence For Adsc's Immunomodulatory Capacity: Cell Culture mentioning

confidence: 99%

Allogeneic and Xenogeneic Transplantation of Adipose-Derived Stem Cells in Immunocompetent Recipients Without Immunosuppressants

Lin

Lue

2012

Stem Cells and Development

187

152

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“…Various studies demonstrated that ADSCs also have the capacity to regulate responses of the immune system (18,19) . They can suppress activation of T-cells by inhibiting expression of cyclin D2 (20) , by inducing regulator T-cells (21) , or by interfering with dentritic cells (21,22) . Additionally, ADSCs may act by means of an anti-apoptotic effect on targetcells, increasing recovery of renal function.…”

Section: Introductionmentioning

confidence: 99%

Role of adipose tissue-derived stem cells in the progression of renal disease

Donizetti-Oliveira

Semedo

Burgos-Silva

et al. 2011

Einstein (São Paulo)

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Objective: To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. Methods: adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105 adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. Results: In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Conclusion: Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

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Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells

Cited by 196 publications

References 41 publications

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Allogeneic and Xenogeneic Transplantation of Adipose-Derived Stem Cells in Immunocompetent Recipients Without Immunosuppressants

Role of adipose tissue-derived stem cells in the progression of renal disease

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