title: Comparable therapeutic potential of umbilical cord mesenchymal stem cells in collagen-induced arthritis to TNF inhibitor or anti-CD20 treatment.
abstract: OBJECTIVE
  The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies.
  
  
  METHODS
  CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring. The frequencies of lymphocytes in spleen were analysed, and serum concentrations of cytokines and autoantibody to CII were also measured. The ability of MSC to regulate the balance of T helper cell subsets in CII stimulated CIA CD4+ T cells was assessed in vitro.
  
  
  RESULTS
  MSC treatment significantly decreased the severity of arthritis, which was comparable to biologic treatments. All the treatments down-regulated Th1 subset. Except anti-CD20 all the treatments decreased Th17 subset. MSC treatment enhanced the proportion of regulatory T (Treg) cells and inhibited the generation of T follicular helper (Tfh) cells. The decrease in autoantibody level was detectable in all the treated groups. In vitro MSC induced Foxp3+ T cells, and down-regulated IL-17+, IFNγ+ T cells and pathogenic IL-17+IFNγ+ or IL-17+Foxp3+ T cells. MSC also reduced the secretion of IL-1β, IL-6, IL-17 and TNF-α among collagen-specific T cells.
  
  
  CONCLUSIONS
  MSC show comparable effects to the known biologic treatments and correct immune imbalance in CIA. MSC might provide a promising approach for the treatment of rheumatoid arthritis.
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Saisai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Huayong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Genhong
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. lingyunsun@nju.edu.cn.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000097:blood; D001688:Biological Products / Q000494:pharmacology*; D002478:Cells, Cultured; D024043:Collagen Type II; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000097:blood; D000068800:Etanercept / Q000494:pharmacology*; D005240:Feasibility Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D008297:Male; D008811:Mice, Inbred DBA; D010641:Phenotype; D011247:Pregnancy; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D001323:Autoantibodies; D001688:Biological Products; D024043:Collagen Type II; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept