Abstract
IntroductionRheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated.MethodsThe effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored.ResultsIn vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-β1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-β1 and NO and UC-MSCs could promote the expansion of CD4+ Foxp3+ regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-α, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA.ConclusionsIn conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.
Highlights
Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction
umbilical cord (UC)-mesenchymal stem cell (MSC) induced hyporesponsiveness of T cells mediated by prostaglandin E2 (PGE2), transforming growth factor b1 (TGF-b1) and Nitric oxide (NO) and umbilical cord MSC (UC-MSC) could promote the expansion of CD4+ Foxp3+ regulatory T cells from RA patients
In conclusion, human UC-MSCs suppressed the various inflammatory effects of fibroblast-like synoviocyte (FLS) and T cells of RA in vitro, and attenuated the development of collagen-induced arthritis (CIA) in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA
Summary
Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. There has been far no report on umbilical cord (UC)-MSCs in the treatment of RA. Rheumatoid arthritis (RA) is a chronic and systemic disease that primarily attacks synovial joints, leading to articular destruction and functional disability. The fibroblast-like synoviocytes (FLSs) are resident cells of synovial joints, involved in pannus formation, and are key players in the destruction of cartilage and bone in RA joint [10]. The ability of FLSs to stimulate both inflammation and tissue damage suggests that this cell type may be another critical target for the treatment of inflammatory arthritis [11]
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