| Abstract: | Objective Bone marrow–derived mesenchymal stem cells (MSCs) can prevent various autoimmune diseases. We examined the therapeutic potential of transforming growth factor β (TGFβ)–transduced MSCs in experimental autoimmune arthritis, using an accepted animal model of collagen‐induced arthritis (CIA). Methods DBA/1J mice with CIA were treated with syngeneic TGFβ‐induced MSCs, whereas control mice received either vehicle or MSCs alone. Arthritis severity was assessed by clinical and histologic scoring. TGFβ‐transduced MSCs were tested for their immunosuppressive ability and differential regulation in mice with CIA. T cell responses to type II collagen were evaluated by determining proliferative capacity and cytokine levels. The effects of TGFβ‐transduced MSCs on osteoclast formation were analyzed in vitro and in vivo. Results Systemic infusion of syngeneic TGFβ‐transduced MSCs prevented arthritis development and reduced bone erosion and cartilage destruction. Treatment with TGFβ‐transduced MSCs potently suppressed type II collagen–specific T cell proliferation and down‐regulated proinflammatory cytokine production. These therapeutic effects were associated with an increase in type II collagen–specific CD4+FoxP3+ Treg cells and inhibition of Th17 cell formation in the peritoneal cavity and spleen. Furthermore, TGFβ‐transduced MSCs inhibited osteoclast differentiation. Conclusion TGFβ‐transduced MSCs suppressed the development of autoimmune arthritis and joint inflammation. These data suggest that enhancing the immunomodulatory activity of MSCs and modulating T cell–mediated immunity using gene‐modified MSCs may be a gateway for new therapeutic approaches to clinical rheumatoid arthritis. |
