title: Preventive effects of CTLA4Ig-overexpressing adipose tissue--derived mesenchymal stromal cells in rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis is a systemic autoimmune disorder. In this study, we first compared the therapeutic effects of syngeneic and xenogeneic adipose tissue-derived stem cells on a collagen-induced arthritis mouse model. Second, we investigated the synergistic preventive effects of CTLA4Ig and adipose tissue-derived mesenchymal stromal cells (ASCs) as a therapeutic substance.
  
  
  METHODS
  Arthritis was induced in all groups except for the normal, saline (N) group, using chicken type II collagen (CII). Animals were divided into C (control, saline), H (hASCs), M (mASCs) and N groups (experiment I) and C, H, CT (CTLA4Ig-overexpressing human ASC [CTLA4Ig-hASCs]) and N groups (experiment II), according to transplanted material. Approximately 2 × 10(6) ASCs or 150 μL of saline was intravenously administered on days 24, 27, 30 and 34, and all animals were killed on days 42 to 44 after CII immunization.
  
  
  RESULTS
  Anti-mouse CII autoantibodies were significantly lower in the H, M and CT groups than in the C group. Cartilage damage severity score and C-telopeptide of type II collagen were significantly lower in the CT group than in the C group. The serum levels of IL-6 were significantly lower in the H, M and CT groups than in the C group. The serum levels of keratinocyte chemoattractant were significantly lower in the CT group than the C group.
  
  
  CONCLUSIONS
  There were similar effects of ASCs on the decrease of anti-mouse CII autoantibody levels between syngeneic and xenogeneic transplantations, and CTLA4Ig-hASCs showed synergistic preventive effects compared with non-transduced hASCs.
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address: vet.cew@gmail.com.
authors.forename: Eun Wha
authors.initials: EW
authors.lastname: Choi
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Yun
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Ji Woo
authors.initials: JW
authors.lastname: Song
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Minjae
authors.initials: M
authors.lastname: Lee
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jehoon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
mesh_terms: D000069594:Abatacept / Q000378:metabolism / Q000627:therapeutic use*; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D001323:Autoantibodies; D064987:Cell- and Tissue-Based Therapy; D024042:Collagen Type I; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides; D013234:Stem Cells; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D024042:Collagen Type I; D024043:Collagen Type II; D015850:Interleukin-6; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D000069594:Abatacept
keywords: CTLA4Ig; adipose tissue–derived mesenchymal stromal cells; autoimmune disease; collagen-induced arthritis; rheumatoid arthritis