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Open Access Highly Accessed Research article

Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis

Yanying Liu1, Rong Mu1, Shiyao Wang1, Li Long1, Xia Liu1, Ru Li1, Jian Sun1, Jianping Guo1, Xiaoping Zhang1, Jing Guo1, Ping Yu1, Chunlei Li1, Xiangyuan Liu2, Zhenyu Huang3, Dapeng Wang3, Hu Li4, Zhifeng Gu5, Bing Liu6 and Zhanguo Li1*

Author Affiliations

1 Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, PR China

2 Department of Rheumatology and Immunology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, PR China

3 Department of Gynecology and Obstetrics, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, PR China

4 Arthritis Clinic and Research Center, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, PR China

5 Department of Rheumatology, The Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, PR China

6 Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, 8 Dong Da Street, Beijing, 100071, PR China

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Arthritis Research & Therapy 2010, 12:R210  doi:10.1186/ar3187

Published: 16 November 2010

Abstract

Introduction

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. 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.

Methods

The 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.

Results

In 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.

Conclusions

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. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.