title: Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100044, PR China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Mu
authors.forename: Shiyao
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Long
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Jianping
authors.initials: J
authors.lastname: Guo
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Huang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D002469:Cell Separation; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D016207:Cytokines