TNF-α modulates the immunosuppressive effects of MSCs on dendritic cells and T cells

Mohammadpour, Hemn; Pourfathollah, Ali Akbar; Zarif, Mahin Nikougoftar; Tahoori, Mohammad Taher

doi:10.1016/j.intimp.2015.07.045

Cited by 34 publications

(34 citation statements)

References 25 publications

(36 reference statements)

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“…In relation with this, Meisel et al have shown that human MSCs exhibit functional IDO activity and inhibit T cell responses upon stimulation with IFN-c in a dose-dependent manner [48]. Exposure of MSCs to inflammatory cytokines have been reported to up-regulate the production of IDO, NO, TGF-b and other anti-inflammatory factors such as hepatocyte growth factor (HGF) [22,49,50] which enhances the therapeutic activity of these cells [51]. Accordingly, English et al illustrated that in non-inflammatory environment, MSCs express low level of IL-10, TGF-b and PGE-2, but following treatment with IFN-c and TNF-a, dramatically express high level of PGE-2 and suppress the lymphocyte proliferation in MLR environment [52].…”

Section: Discussionmentioning

confidence: 99%

“…Also, Crop et al have shown that there was no up-regulation of antiinflammatory factors: IL-10, TGF-b and inducible nitric oxide synthase (iNOS) by MSCs after culture with pro-inflammatory cytokines [20]. On the other hand, there are some reports that inflammatory cytokine-stimulation of MSCs increases the TGF-b production [22,23,50]. Since, TGF-b is a tissue-repairing and antiinflammatory cytokine with known potency to induce angiogenesis, reduce inflammatory signaling and enhancement of MSCs differentiation [58][59][60][61]; based on our results, pre-treatment of MSCs with pro-inflammatory cytokines could enhance MSC-mediated tissue regeneration and repair activity.…”

Section: Discussionmentioning

confidence: 99%

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The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

et al. 2016

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“…They actively regulate macrophages, 17,18 neutrophils, 19,20 dendritic cells, 21-23 and natural killer cells, 24,25 thereby modulating the first line of defense. MSCs also regulate the adaptive immune system, i.e., B and T lymphocytes.…”

Section: Immunosuppressive Properties Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

et al. 2016

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Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs’ unique ability to modulate inflammation, and both innate and adaptive immunity.

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“…To select best candidate for AD-MSCs preactivation, we checked the immunosuppressive properties of AD-MSCs after MSCs activation either by TNF-α, IFN-γ or TNF-α plus IFN-γ. Our previous data indicated that TNF-α modulates the immunosuppressive effects of AD-MSCs on T cells and Dendritic cells compared to IFN-γ and IFN-γ plus TNF-α16. Moreover, we evaluated the expression of CD271 as a marker which displays the potent immunosuppressive AD-MSCs17.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, enhanced level of TGF-β and PGEF in tumor cells can directly contribute to the development of Treg cells in tumor microenvironment6.In preactivated MSCs, it seems that high level of apoptosis induction decreased the tumor cell mass as a main source of soluble factor release which in turn recruit MSCs and induce Treg cells. Moreover, some studies showed that TNF-α modulated the immunosuppressive effects of MSCs1646.…”

Section: Discussionmentioning

confidence: 99%

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model

Mohammadpour

Pourfathollah

Zarif

et al. 2016

Sci Rep

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Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.

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TNF-α modulates the immunosuppressive effects of MSCs on dendritic cells and T cells

Cited by 34 publications

References 25 publications

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model

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