|Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis|
|Liu, Yanying1; Mu, Rong1; Wang, Shiyao1; Long, Li1; Liu, Xia1; Li, Ru1; Sun, Jian1; Guo, Jianping1; Zhang, Xiaoping1; Guo, Jing1; Yu, Ping1; Li, Chunlei1; Liu, Xiangyuan2; Huang, Zhenyu3; Wang, Dapeng3; Li, Hu4; Gu, Zhifeng5; Liu, Bing6; Li, Zhanguo1|
|刊名||ARTHRITIS RESEARCH & THERAPY|
|WOS标题词||Science & Technology|
|关键词[WOS]||COLLAGEN-INDUCED ARTHRITIS ; REGULATORY T-CELLS ; FIBROBLAST-LIKE SYNOVIOCYTES ; BONE-MARROW ; BIOLOGICS-REGISTER ; TNF-ALPHA ; RESPONSES ; DISEASE ; AUTOIMMUNE ; PROLIFERATION|
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 beta 1 (TGF-beta 1) 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-beta 1. 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-beta 1 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-alpha, 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.
|项目编号||2010 CB 529100 ; 2008BAI59B01 ; 30972710 ; RDB 2009-05|
|资助机构||National Basic Research Program of China ; Key Projects in the National Science & ; Technology Pillar Program in the Eleventh Five-year Plan Period ; National Sciences Foundation of China ; Peking University People&prime ; s Hospital|
|作者单位||1.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China|
2.Peking Univ, Hosp 3, Dept Rheumatol & Immunol, Beijing 100191, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Gynecol & Obstet, Beijing 100044, Peoples R China
4.Peking Univ, Peoples Hosp, Arthrit Clin & Res Ctr, Beijing 100044, Peoples R China
5.Nantong Univ, Affiliated Hosp, Dept Rheumatol, Nantong 226001, Peoples R China
6.Acad Mil Med Sci, Affiliated Hosp, Lab Oncol, Beijing 100071, Peoples R China
|Liu, Yanying,Mu, Rong,Wang, Shiyao,et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis[J]. ARTHRITIS RESEARCH & THERAPY,2010,12(6).|
|APA||Liu, Yanying.,Mu, Rong.,Wang, Shiyao.,Long, Li.,Liu, Xia.,...&Li, Zhanguo.(2010).Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis.ARTHRITIS RESEARCH & THERAPY,12(6).|
|MLA||Liu, Yanying,et al."Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis".ARTHRITIS RESEARCH & THERAPY 12.6(2010).|