Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells

Glennie, Sarah; Soeiro, Inês; Dyson, P. Julian; Lam, Eric W.‐F.; Dazzi, Francesco

doi:10.1182/blood-2004-09-3696

Cited by 1,044 publications

(843 citation statements)

References 34 publications

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“…Thus, it did not appear to be dependent on the induction of apoptosis of proliferating cells [13,16,39]. Inhibition of cell division could be a possible explanation since accumulation of cells in the G 0 phase of the cell cycle has been detected [45]. In addition, suppression of T cell proliferation induced by human MSC appears to depend, at least in part, on the cross-talk between the two cell populations, leading to the production of inflammatory cytokines such as IFN-c [39] and IL-1b [37] by activated immune cells.…”

Section: Msc and T Lymphocytesmentioning

confidence: 95%

“…In mouse experiments, B lymphocytes were enriched from splenocyte suspensions and activated in vitro using T cell-dependent stimuli. In this context, Glennie et al used an anti-CD40 mAb and IL-4 [45], while Augello et al stimulated splenic B cells with pokeweed mitogen [49]. Both studies reached the same conclusion, i.e.…”

Section: Msc and B Cellsmentioning

confidence: 98%

“…In addition, suppression of T cell proliferation induced by human MSC appears to depend, at least in part, on the cross-talk between the two cell populations, leading to the production of inflammatory cytokines such as IFN-c [39] and IL-1b [37] by activated immune cells. Inhibition of T cell proliferation resulted in the decreased production of effector Th1 cytokines [16,42,46]; however, the expression of activation markers in T cells that have been cultured with MSC remains a controversial issue [39,43,45,47]. Inhibition of T cell proliferation by MSC appears to be subsequent both to cell-to-cell interaction and to the release of soluble factors, and it is conceivable that discrepant findings reported in the literature reflect differences in the experimental conditions used [13,14,16,48,49].…”

Section: Msc and T Lymphocytesmentioning

confidence: 99%

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Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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Section: Msc and T Lymphocytesmentioning

confidence: 95%

Section: Msc and B Cellsmentioning

confidence: 98%

Section: Msc and T Lymphocytesmentioning

confidence: 99%

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Immunoregulatory function of mesenchymal stem cells

2006

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“…Besides their capacity to differentiate into mesenchymal and nonmesenchymal cell lineages (7,8) and their potential clinical application for the repair of damaged tissues, several recent studies have shown that bone marrow-derived MSCs (BM-MSCs) regulate the immune response, including in vitro inhibition of T cell proliferation, B cell function, and dendritic cell maturation (9)(10)(11)(12)(13). Some researchers have reported the use of BM-MSCs to treat allograft rejection and acute graftversus-host disease as well as to alleviate experimental autoimmune encephalomyelitis, collagen-induced arthritis (CIA), and autoimmune myocarditis (11,(14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

González¹,

González‐Rey²,

Rico³

et al. 2009

Arthritis & Rheumatism

453

363

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Objective. Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Adult mesenchymal stem cells (MSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. The purpose of this study was to examine a new therapeutic strategy for RA based on the administration of human adipose-derived MSCs (AD-MSCs).Methods. DBA/1 mice with collagen-induced arthritis were treated with human AD-MSCs after disease onset, and clinical scores were determined. Inflammatory response was determined by measuring the levels of different mediators of inflammation in the joints and serum. The Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with the autoantigen. The number of Treg cells and the suppressive capacity on self-reactive Th1 cells were also determined.Results. Systemic infusion of human AD-MSCs significantly reduced the incidence and severity of experimental arthritis. This therapeutic effect was mediated by down-regulating the 2 deleterious disease components: the Th1-driven autoimmune and inflammatory responses. Human AD-MSCs decreased the production of various inflammatory cytokines and chemokines, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of antiinflammatory interleukin-10 in lymph nodes and joints. Human ADMSCs also induced de novo generation of antigenspecific CD4؉CD25؉FoxP3؉ Treg cells with the capacity to suppress self-reactive T effector responses.Conclusion. Human AD-MSCs emerge as key regulators of immune tolerance by inducing the generation/activation of Treg cells and are thus attractive candidates for a cell-based therapy for RA.

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“…However, the implementation of the SCNT tech-nique to derive autologous ESCs remains highly controversial and is unlikely to become a routine procedure in the foreseeable future (46). In addition, the logic for development of such therapy remains contentious, in view of the recent studies showing that allogeneic/ xenogeneic MSCs have immunomodulatory properties (47) and can be safely transplanted without obvious untoward toxic effects and without the possibility of immune rejection, at least in specific experimental model systems (48,49). MSCs are currently being tested in clinical settings to ascertain whether, in fact, tissue rejection can be prevented (50,51).…”

Section: Stem Cells and Immunitymentioning

confidence: 99%

Lessons from musculoskeletal stem cell research: The key to successful regenerative medicine development

McGonagle

Bari

Arnold

et al. 2007

Arthritis & Rheumatism

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Polystyrene and poly(butyl acrylate) were grafted from silicon wafer surface by reversible addition‐fragmentation chain transfer (RAFT) polymerization. Three RAFT agents were immobilized onto silicon wafer through their leaving/initiating groups (R group). Grafting polymerization of butyl acrylate (BA) and styrene (St) was then carried out from the immobilized RAFT agents. The immobilization of the RAFT agents and the subsequent grafting polymerization of St and BA were evaluated by ellipsometry and X‐ray photoelectron spectroscopy. It was found that type of monomer, structure of RAFT agent, and local RAFT concentration on the surface have dramatic influences on the thickness of grafted polymer layer. The grafting polymerization with more severe rate retardation effect yielded thinner polymer films on the silicon wafer. Selection of a RAFT agent with little rate retardation was critical in the grafting polymerization to achieve thick films. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 970–978, 2008

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Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells

Cited by 1,044 publications

References 34 publications

Immunoregulatory function of mesenchymal stem cells

Immunoregulatory function of mesenchymal stem cells

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

Lessons from musculoskeletal stem cell research: The key to successful regenerative medicine development

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