Page 92 - Power of Stem Cells- arthritis and regeneration

Liu et al. Arthritis Research & Therapy 2010, 12:R210
http://arthritis-research.com/content/12/6/R210

RESEARCH ARTICLE Open Access

Therapeutic potential of human umbilical cord

mesenchymal stem cells in the treatment of

rheumatoid arthritis

1†
1†
1
1
1
1
1
1
1
Yanying Liu , Rong Mu , Shiyao Wang , Li Long , Xia Liu ,RuLi , Jian Sun , Jianping Guo , Xiaoping Zhang ,
2
1
1
1
3
4
3
5
6
Jing Guo , Ping Yu , Chunlei Li , Xiangyuan Liu , Zhenyu Huang , Dapeng Wang ,HuLi , Zhifeng Gu , Bing Liu ,
Zhanguo Li 1*
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 b1 (TGF-b1) 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-
b1. 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-b1 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-a, 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.
Introduction new target therapies have achieved considerable success.
Rheumatoid arthritis (RA) is a chronic and systemic disease For instance, TNF-a inhibitors and B-cell-depleting thera-
that primarily attacks synovial joints, leading to articular pies have benefited many RA patients [1,2]. However, these
destruction and functional disability. RA imparts a massive approaches are expensive and none of the currently widely
burden on health services worldwide. Efforts to discover used biological agents reaches longterm drug-free remis-
sion [3,4]. Therefore, it is important to develop new and
* Correspondence: Zgli98@yahoo.com more effective therapy for RA.
† Contributed equally
1 In RA, proinflammatory cytokines, such as TNF-a,IL-6,
Department of Rheumatology and Immunology, Peking University People’s
Hospital, 11 Xizhimen South Street, Beijing, 100044, PR China IL-1b and IL-17, play dominant pathological roles.
Full list of author information is available at the end of the article
© 2010 Liu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.