Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis.

Zheng, Zhaohui; Li, X. Y.; Ding, Jin; Jia, Jun; Zhu, Ping

doi:10.1093/rheumatology/kem284

Cited by 144 publications

(109 citation statements)

References 41 publications

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“…As Fig. 5 shows, in the presence of MSCs from P1, PHA-stimulated T-cell proliferation was significantly inhibited (89.7±3.5% in the presence of MSCs, P<0.001) compared to the no MSCs group with the stimulation of PHA, which is in accordance with our previous study (13). However, the inhibitory capacity of MSCs decreased with their successive expansion in vitro.…”

Section: Effects Of Mscs In Long-term Culture On the Proliferation Ofsupporting

confidence: 89%

“…After every 6th passage, some of the expanded cells were separated for studying. The adherent cells derived from the 5 donors were all identified as MSCs according to the method described in our previous report (13).…”

Section: Methodsmentioning

confidence: 99%

“…On the basis of these findings, some researchers employed MSCs to treat experimental autoimmune encephalomyelitis (EAE) and successfully alleviated this T-cell-mediated autoimmune disease in an animal model (12). Furthermore, our group recently demonstrated that MSCs could exert profound suppressive effects on type II collagen-reactive T cells from rheumatoid arthritis (RA) patients (13). Improved knowledge of these immunological properties of MSCs creates a potential cellimmunotherapeutic approach for arthritic diseases, and MSCs have also been gaining attention from rheumatologists (14).…”

Section: Introductionmentioning

confidence: 99%

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Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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Abstract. Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA β-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).

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Section: Effects Of Mscs In Long-term Culture On the Proliferation Ofsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Ding

Zheng

et al. 2012

Molecular Medicine Reports

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“…Similar effects have been observed in experimental models of rheumatoid arthritis where MSCs alone, 72,73 or genetically modified overexpressing IL10, 74 prevented tissue destruction and suppressed the autoimmune response against type II collagen.…”

Section: Animal Models Of Autoimmunitysupporting

confidence: 74%

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

Tyndall

Uccelli

2009

Bone Marrow Transplant

106

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“…Human MSCs obtained from subcutaneous adipose tissue (AD-MSCs) have recently emerged as an attractive alternative source of MSCs for cell therapy (7,8,10,21). Large amounts of human AD-MSCs can be easily obtained from lipoaspirates from healthy donors and rapidly expanded in vitro to generate a clinically effective dosage, and recent studies have reported that human AD-MSCs share some of the immunomodulatory properties that characterize the BM-MSCs (18,22,23).…”

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

447

357

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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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Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis.

Abstract: Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.

Cited by 144 publications

References 41 publications

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

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

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