Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis

Ma, Ding; Xu, Ke; Zhang, Gailian; Liu, Yang; Gao, Jinfang; Tian, Mingyi; Chi, Chun‐Wei; Li, Juan; Zhang, Liyun

doi:10.1016/j.intimp.2019.105687

Cited by 70 publications

(52 citation statements)

References 28 publications

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“…The ability of MSCs to favor CD4 + CD25 + FoxP3 + Treg cells' differentiation and/or enhance their activity is broadly described in the literature, and some of the mechanistic basis of these processes are also well elucidated (Duffy, Ritter, Ceredig, & Griffin, ; Griffin, Ritter, & Mahon, ). Recent studies give further evidences that human MSCs support the induction of Treg polarization either in PBMCs from RA patients in vitro (Ma et al, ), as well as in collagen‐induced arthritis mice model, both in vitro and in vivo (Kay et al, ; Ma et al, ; Nam et al, ; Yu et al, ). Nevertheless, MSCs are also known to be highly sensitive to the surrounding microenvironment; accordingly, different conditions in the experimental protocols of in vitro or in vivo assays are likely to affect MSCs immunomodulatory behavior.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, we may hypothesize that, under our experimental conditions, a 24‐hr coculture period of PBMCs and MSCs was not long enough for Treg cell polarization process to be completed, or MSCs used alternative immunomodulatory mechanisms different from Treg induction. The classical in vitro protocols for Treg generation with TGF‐β plus IL‐2 comprise a 3–6 day cell culture period and, in the abovementioned studies (Kay et al, ; Ma et al, ; Nam et al, ; Yu et al, ), the detection of Treg cells was evaluated after 3 days to 6 weeks of exposure to MSCs. In this line, our experimental protocol demonstrates that MSCs may exert an early immunosuppressive activity independent of Treg cell induction.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Pedrosa

Gomes

Laranjeira

et al. 2019

J Tissue Eng Regen Med

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Rheumatoid arthritis (RA) is a Th1/Th17‐mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease‐modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)‐MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4+ and CD8+ T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM‐MSCs. The expression of (interleukin) IL‐2, tumor necrosis factor alpha (TNF‐α), and interferon‐gamma (IFN‐γ) was evaluated in naive, central memory, effector memory, and effector CD4+ and CD8+ T cells, whereas IL‐6, IL‐9, and IL‐17 expression was measured in total CD4+ and CD8+ T cells. mRNA expression of IL‐4, IL‐10, transforming growth factor beta (TGF‐β), cytotoxic T‐lymphocyte‐associated antigen 4, and/or forkhead box P3 was quantified in fluorescence‐activated cell sorting‐purified CD4+ T cells, CD8+ T cells, and CD4+ Treg. BM‐MSCs inhibited the production of TNF‐α, IL‐17, IL‐6, IL‐2, IFN‐γ, and IL‐9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM‐MSCs increased expression of IL‐10 and TGF‐β by CD4+ and CD8+ T cells. BM‐MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM‐MSC‐derived immunomodulation affected either naive, effector, and memory T cells.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Pedrosa

Gomes

Laranjeira

et al. 2019

J Tissue Eng Regen Med

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“…Stem cells are cells with multidifferentiation capacity that exert immunomodulatory effects by modulating T and B cell proliferation and differentiation, dendritic cell maturation, and natural killer (NK) cell activity (Naik et al, 2018). In addition to their self-renewal ability, human umbilical mesenchymal stem cells (HUMSCs) exhibit minimal immune rejection and can be used for allogeneic transplantation (Ma et al, 2019). The abovementioned characteristics indicate the potential of using HUMSCs to treat autoimmune diseases (ADs), and this finding has been verified (Uccelli et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Lü

Fan

et al. 2020

Front. Cell Dev. Biol.

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Background: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA). Method: HUMSCs (1 × 10 6) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated. Results: HUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely,

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“…Cytotherpy therapy with mesenchymal stem cells (MSCs) has been attempted in many other model of inflammatory disease, such as inflammatory bowel disease, peritonitis and rheumatoid arthritis [9][10][11]. MSCs are a heterogeneous population of pluripotent cells that can be obtained and expanded ex vivo from different tissues.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells reduce alcoholic hepatitis in mice via suppression of hepatic neutrophil and macrophage infiltration, and of oxidative stress

Wan

Liu

et al. 2020

PLoS ONE

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Mesenchymal stem cells (MSCs) are a population of pluripotent cells that have been tested for the treatment of many inflammatory diseases. It remains unclear whether MSCs were effective in treating mice with alcoholic hepatitis (AH) and its underlying mechanism. In the present study, MSCs were isolated from bone marrow of 4-6 week-old C57BL/6N male mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) transplantation of MSCs or saline were performed in mice on day 10. Blood samples and hepatic tissues were harvested on day 11. Biochemical, liver histological and flow cytometric analyses were performed. Compared to the control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC)

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Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis

Cited by 70 publications

References 28 publications

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Mesenchymal stem cells reduce alcoholic hepatitis in mice via suppression of hepatic neutrophil and macrophage infiltration, and of oxidative stress

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