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.
Original language | English (US) |
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Pages (from-to) | 1668-1680 |
Number of pages | 13 |
Journal | Arthritis and rheumatism |
Volume | 63 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2011 |
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
- Pharmacology (medical)