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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 treatment 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 therapy 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 therapy 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.

URL: http://onlinelibrary.wiley.com/doi/10.1002/art.30474/full

* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 12-03-2014