From bench to bedside of mesenchymal stem cells use for rheumatoid arthritis treatment

Mesenchymal stem cells (MSCs) are multipotent stem cells with immuno- suppressive properties able to control both the innate and the adaptive immune system. Based on this latter characteristic, MSC-based therapies have become a thriving area for autoimmune diseases such as rheumatoid arthritis (RA). RA is a chronic inflam- matory disorder that involves an imbalance of both the innate and adaptive immune systems, which leads to cartilage and bone degradations, causing pain, stiffness, and synovitis. Several studies have reported the beneficial effects of MSCs in experimen- tal models of arthritis. However, the complexity of RA as well as the controversy about the mechanisms and molecules involved in the immunosuppressive effect of MSCs, together with the low efficacy showed on clinical trials, have generated inse- curity around its therapeutic use, and for this reason it is necessary to increase the number of investigations. In this context, enhancement of MSC immunosuppressive potential, in order to obtain a stable suppressive phenotype, offers a powerful tool to improve MSC-based therapies. Thus, the aim of this review is to discuss the cross talk between MSCs and the intricate pathogenesis of RA and the possible molecular targets that could lead to improve their therapeutic potential on RA progression.