Role of mesenchymal stem cells in reestablishing immunologic tolerance in autoimmune rheumatic diseases
The process of immunologic tolerance is critical in preventing autoimmune disease and maintaining immune system homeostasis. Increased understanding regarding cytokine networks has led to the development of neutralizing antibodies against tumor necrosis factor α (TNFα) and against interleukin-1 (IL-1) and IL-6 signaling in the results of rheumatoid arthritis (RA). However, there remains an unmet need, given the significant number of patients not achieving remission or whose condition fails to respond to these drugs. Mesenchymal (stromal) stem cells (MSCs) are promising tools for the repair of damaged joint tissue such as cartilage, bone, and tendons. Moreover, MSCs have potent antiinflammatory and immunomodulatory properties, both in vitro and in vivo (1). Research into MSC for Crohn’s disease, type 1 diabetes mellitus, graft-versus-host disease (GVHD), and multiple sclerosis continues apace with ongoing phase II/III trials (http://www.clinicaltrials.gov). There have been conflicting reports regarding the effects of MSCs in autoimmune rheumatic diseases, particularly in the collagen-induced arthritis (CIA) mouse model of RA (2–8). Conversely, promising results in patients with systemic lupus erythematosus (SLE) were recently reported (9), even in the face of conflicting results in murine models of SLE.
In the present review, we examine MSCs as a possible cellular for RA, SLE, and systemic sclerosis (SSc), and critically assess possible reasons for conflicting results in the literature. We also address whether MSC dysfunction could play a role in the pathogenesis of these conditions. Finally, we examine the possible mechanisms of action of MSCs at the cellular level, including their effects on Treg cells and Th17 cell populations.