title: Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice.
abstract: Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.
authors: Division of Rheumatology, Department of Internal Medicine, Pochon CHA University, Sungnam, Korea.
authors: J-J
authors: JJ
authors: Choi
authors: S-A
authors: SA
authors: Yoo
authors: S-J
authors: SJ
authors: Park
authors: Y-J
authors: YJ
authors: Kang
authors: W-U
authors: WU
authors: Kim
authors: I-H
authors: IH
authors: Oh
authors: C-S
authors: CS
authors: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000601:surgery*; D049109:Cell Proliferation; D024043:Collagen Type II / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007074:Immunoglobulin G / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D024043:Collagen Type II; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4