Transplantation of gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic, progressive, and inflammatory autoimmune disease which primarily affects the small arthrodial joints. The aim of this study was to test whether transplantation of mesenchymal stem cells derived from gingival tissue (GMSCs) could ameliorate collagen-induced arthritis (CIA), and to explore the role of the FasL/Fas pathway in the underlying mechanism. Methods: DBA/1 mice with collagen II-induced arthritis were treated with GMSCs from the C57BL/6 J mouse, the B6Smn.C3-FasLgld/J mouse (FasL-/- GMSCs), and FasL overexpressed FasL-/- GMSCs (FasL TF GMSCs). Inflammation was evaluated by measuring clinical score, tumor necrosis factor (TNF)-α and anti-collagen II antibody levels, and histological analyses. The levels of CD4+ Th cell subsets in spleens and draining lymph nodes were assessed by flow cytometric analysis. Results: Systemic infusion of GMSCs can significantly reduce the severity of experimental arthritis, and resume the balance of Th cell subsets. FasL-/- GMSCs failed to induce apoptosis of activated T cells in vitro and in vivo, and therefore show no therapeutic effects, whereas FasL TF GMSCs can rescue the immunosuppressant effects in the treatment of CIA. Conclusions: GMSC-based therapy induces T-cell apoptosis via the FasL/Fas pathway and results in immune tolerance and amelioration of the CIA inflammation.