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Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatory T cells in vitro in rheumatoid arthritis
  1. Elena Gonzalez-Rey (elenag{at}
  1. School of Medicine, Seville University, Seville, Spain
    1. Manuel A Gonzalez
    1. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
      1. Nieves Varela
      1. Instituto de Parasitologia y Biomedicina, CSIC, Granada, Spain
        1. Francisco O'Valle
        1. School of Medicine, University of Granada, Spain
          1. Pedro Hernandez-Cortes
          1. San Cecilio University Hospital, Spain
            1. Laura Rico
            1. Cellerix, SA, Madrid, Spain
              1. Dirk Büscher
              1. Cellerix, SA, Madrid, Spain
                1. Mario Delgado (mdelgado{at}
                1. Instituto de Parasitologia y Biomedicina, CSIC, Granada, Spain


                  Objectives: Adult mesenchymal stem cells were recently found to suppress effector T-cell and inflammatory responses and have emerged as attractive therapeutic candidates for immune disorders. In rheumatoid arthritis (RA), a loss in the immunological self-tolerance causes the activation of autorreactive T cells against joint components and subsequent chronic inflammation. The aim of this study is to characterize the immunosuppresive activity of human adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T cells from RA patients.

                  Methods: We investigated the effects of hASCs on collagen-reactive RA human T-cell proliferation and cytokine production, as well as on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from RA patients.

                  Results: hASCs suppressed antigen-specific response of T cells from RA patients. hASCs inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. In contrast, the number of IL-10-producing T cells and monocytes significantly augmented upon hASC-treatment. The suppressive activity of hASCs was both cell-to-cell contact-dependent and -independent. hASCs also stimulated the generation of FoxP3-expressing CD4+CD25+ regulatory T cells with capacity to suppress collagen-specific T-cell responses. Finally, hASCs donwregulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from RA patients.

                  Conclusions: Our work identifies to hASCs as key regulators of immune tolerance with capacity to suppress T-cell and inflammatory responses to induce the generation/activation of antigen-specific regulatory T cells.

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