title: The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system.
abstract: BACKGROUND
  Previous in vivo studies have shown that mesenchymal stem cell (MSC) transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus.
  
  
  METHODS
  To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA). Orphan nuclear receptor gamma (ROR-γ) mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF-α) in the cell culture supernatant were measured using a flow cytometric bead capture method.
  
  
  RESULTS
  After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p < 0.05). Moreover, the decrement was positively related to the disease activity of RA (p < 0.05). Decreased secretion of IL-17, TNF-α and IL-6 were also found in co-culture supernatants of PBMCs from patients with severe and moderate disease activity, but not in supernatant from PBMCs cultured alone. The decreased cytokine expression levels were positively correlated to the concentrations of MSCs. In contrast, PBMCs from healthy controls or patients with mild RA did not show significant differences in ROR-γ expression or cytokine secretion following co-culture with MSCs as compared with those cultured alone.
  
  
  CONCLUSIONS
  In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators.
authors.affiliation: The Second Hospital Affiliated of Shanxi Medical University, Shanxi, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Lihui
authors.initials: L
authors.lastname: Ma
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Lv
authors.forename: Lijin
authors.initials: L
authors.lastname: Xue
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D019899:Paracrine Communication; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D014409:Tumor Necrosis Factor-alpha