Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Engela, A.U.; Baan, Carla C.; Litjens, Nicolle H.R.; Franquesa, Marcella; Betjes, Michiel G. H.; Weimar, Willem; Hoogduijn, Martin J.

doi:10.1111/cei.12199

Cited by 42 publications

(35 citation statements)

References 66 publications

(86 reference statements)

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“…This study supports the hypothesis that CD8 + T cells, found at a high frequency in the inflammatory joints, could play a role in RA pathogenesis [76]. MSCs are able to suppress CD8 + activation in vitro [77]. Moreover, it has been recently described that MSCs are able to induce the generation of CD8 + CD28 − Treg cells and also enhance their ability to suppress CD4 + T cell proliferation and activation [78].…”

Section: Adaptive Immunity In Ra and The Effect Of Mscssupporting

confidence: 85%

Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Contreras-López

Figueroa

Djouad

et al. 2016

Stem Cells International

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Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

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Section: Adaptive Immunity In Ra and The Effect Of Mscssupporting

confidence: 85%

Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Contreras-López

Figueroa

Djouad

et al. 2016

Stem Cells International

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“…In contrast to the several hundred studies demonstrating MSC immunosuppression of CD4 T cells, only a handful of reports have focused on MSC interactions with CD8 T cells. While a few studies have demonstrated that tissue‐resident MSCs can suppress CD8 T proliferation and cytotoxicity , other reports have shown inconsistent MSC regulation of Tc1 and only one report found inhibition of Tc17 by MSCs . Our study is the first to demonstrate that all sources of MSCs tested including iPSC‐MSCs are strongly immunomodulatory toward CD8 T cells, suppressing effector functions including perforin expression as well as specifically Tc1 and Tc17 subpopulations.…”

Section: Discussionmentioning

confidence: 49%

Differentiation of Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Results in Downregulation of c-Myc and DNA Replication Pathways with Immunomodulation Toward CD4 and CD8 Cells

Wang

Jiang²,

Ting

et al. 2018

Stem Cells

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Multilineage tissue-source mesenchymal stem cells (MSCs) possess strong immunomodulatory properties and are excellent therapeutic agents, but require constant isolation from donors to combat replicative senescence. The differentiation of human induced pluripotent stem cells (iPSCs) into MSCs offers a renewable source of MSCs; however, reports on their immunomodulatory capacity have been discrepant. Using MSCs differentiated from iPSCs reprogrammed using diverse cell types and protocols, and in comparison to human embryonic stem cell (ESC)-MSCs and bone marrow (BM)-MSCs, we performed transcriptome analyses and assessed for functional immunomodulatory properties. Differentiation of MSCs from iPSCs results in decreased c-Myc expression and its downstream pathway along with a concomitant downregulation in the DNA replication pathway. All four lines of iPSC-MSCs can significantly suppress in vitro activated human peripheral blood mononuclear cell (PBMC) proliferation to a similar degree as ESC-MSCs and BM-MSCs, and modulate CD4 T lymphocyte fate from a type 1 helper T cell (Th1) and IL-17A-expressing (Th17) cell fate to a regulatory T cell (Treg) phenotype. Moreover, iPSC-MSCs significantly suppress cytotoxic CD8 T proliferation, activation, and differentiation into type 1 cytotoxic T (Tc1) and IL-17-expressing CD8 T (Tc17) cells. Coculture of activated PBMCs with human iPSC-MSCs results in an overall shift of secreted cytokine profile from a pro-inflammatory environment to a more immunotolerant milieu. iPSC-MSC immunomodulation was also validated in vivo in a mouse model of induced inflammation. These findings support that iPSC-MSCs possess low oncogenicity and strong immunomodulatory properties regardless of cell-of-origin or reprogramming method and are good potential candidates for therapeutic use. Stem Cells 2018;36:903-914.

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“…In addition, MSCs can modulate T lymphocyte fate, polarizing naïve CD4 towards a regulatory T cell (Treg) phenotype and shifting the cytokine profile from a T helper cell type 1 (Th1)—in which high levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are secreted—to a Th2 milieu [22]. MSCs can suppress the cytotoxic activity of CD8 cytotoxic T cells [23, 24] as well as natural killer cells (NK) [25], and can also interfere with B cell maturation and antibody production [26, 27]. In addition to interacting with adaptive and innate lymphocyte populations, MSCs have also been shown to modulate the differentiation, expansion, and/or function of myeloid cells towards more immunosuppressive and immunomodulatory phenotypes.…”

Section: Clinical Status Of Msc Therapy For Immune-/inflammation-medimentioning

confidence: 99%

Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials

et al. 2016

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Human mesenchymal stem cells (MSCs) are multilineage somatic progenitor/stem cells that have been shown to possess immunomodulatory properties in recent years. Initially met with much skepticism, MSC immunomodulation has now been well reproduced across tissue sources and species to be clinically relevant. This has opened up the use of these versatile cells for application as 3rd party/allogeneic use in cell replacement/tissue regeneration, as well as for immune- and inflammation-mediated disease entities. Most surprisingly, use of MSCs for in immune-/inflammation-mediated diseases appears to yield more efficacy than for regenerative medicine, since engraftment of the exogenous cell does not appear necessary. In this review, we focus on this non-traditional clinical use of a tissue-specific stem cell, and highlight important findings and trends in this exciting area of stem cell therapy.

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Mesenchymal stem cells control alloreactive CD8+CD28− T cells

Cited by 42 publications

References 66 publications

Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

Differentiation of Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Results in Downregulation of c-Myc and DNA Replication Pathways with Immunomodulation Toward CD4 and CD8 Cells

Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials

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