Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis.
Liu, Yanying, Mu, Rong, Wang, Shiyao, Li, Zhanguo
Rheumatoid arthritis (RA) is a T-cell-mediated systematic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells 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, potent immunosuppressive effects of human UC-MSCs in RA were evaluated.
The effects of UC-MSCs on responses of 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 factorb1 (TGF-b1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs in collagen-induced arthritis (CIA) in mice model were explored.
In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-b1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. Albeit inducing hyporesponsiveness of T cells mediated by PGE2, TGF-b1 and NO, 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 mice model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-a, IL-6 and MCP-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.
In 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.
To cite this abstract, please use the following information:
Liu, Yanying, Mu, Rong, Wang, Shiyao, Li, Zhanguo; Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1134