Human mesenchymal stem cells as a tool for joint repair in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterised with chronic inflammatory synovitis and progressive joint. Because damaged and/or deformed joints cannot be repaired, a novel treatment strategy aimed at both anti-inflammation and bone regeneration is a prerequisite. Mesenchymal stem cells (MSCs) can be easily isolated from various organs and possess multipotent capacity and exhibit immunoregulatory properties. Using human MSC derived from bone marrow and adipose tissue, we have clarified the following novel findings in vitro. 1) MSCs differentiated into osteoblasts or osteocytes under osteoblast-conditioned medium including the inflammatory stimuli such as IL-1. 2) The combination of IL-6 and soluble IL-6 receptor induced differentiation of MSCs to chondrocyte. 3) MSCs produced osteoprotegerin and inhibited osteoclastogenesis. Furthermore, we developed a local delivery system of MSCs by using nano-fibre scaffold. MSCs seeded on nano-fibre scaffold suppressed arthritis and joint destruction by inhibiting systemic inflammatory reaction and immune response through the induction of regulatory T cells and subsequent reduction in the production of anti-type II collagen antibody in vivo. Thus, our data may serve as a new strategy for MSC-based therapy in inflammatory diseases and an alternative delivery method for the treatment of damaged joints in RA.