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Stem Cell Applications In Rheumatic Diseases

09 February 2017

Mesenchymal stem cells (MSC) have been used in animal models and in many in vitro studies for various diseases, including rheumatic diseases, for the past decade. The first successful outcome after MSCs were started being used for therapeutic purposes was achieved 15 years ago in support of the efficacy of bone marrow transplant. However, the actual boom in this field has been observed following the publication of the achievements of these cells in cases of acute graft versus host disease since 2004.

Recently, a better understanding of the MCS functions showed that these cells also have strong immunosuppressive and inflammatory suppressive effects. Mesenchymal stem cells have been proposed as a promising alternative in the treatment of many rheumatic diseases, especially rheumatoid arthritis (RA), thanks to their immunoregulatory functions.

Rheumatoid arthritis 

The first publication about the use of MSC in rheumatoid arthritis belonged to the transplantation and negative results of MSC of allogenic bone marrow in four patients. 172 patients participated in the second major study on patients with rheumatoid arthritis, and 136 patients were given 40x106 allogenic umbilical cord-derived MSC, while 36 patients were given cell-free culture fluid as placebo. There were two treatment options in this study: One of the options was to give cell-free culture fluid with non-steroidal anti-inflammatory drugs that modify the disease (control group) and the other one was to give umbilical cord MSC in addition to the other drugs. At the end of the study, the researchers concluded that the fluid given had no benefit in control group patients and the umbilical cord MSC therapy, which was given in addition to non-steroidal anti-inflammatory drugs for patients with rheumatoid arthritis, was clinically reliable, significant, and permanent. In addition to these studies, positive outcomes were notified in three patients, who received autologous adipose-derived MSC in 2011.

Dermatomyositis / Polymyositis (DM/PM) 

Some of the 10 patients with therapy-resistant DM / PM or severe systemic involvement were infused intravenous allogenic bone marrow-derived MSC and some were infused umbilical cord-derived MSC 106 cells/kg. Partial clinical improvement and decrease in creatinine kinase level were seen in all cases. Patients who developed a relapse received a second infusion. A 35-year old female with significant improvement received 4 infusions of adipose tissue-derived MSCs that were reproduced in a culture environment.

Systemic Sclerosis 

The first report on the use of MSC in the treatment of a rheumatic disease belonged to a 41-year old female in 2008. Following single dose infusion of intravenous allogenic MSC (106 cell/kg), a significant improvement is noted on skin and in ulcers of this patient who was diagnosed with complicated diffuse cutaneous systemic sclerosis 4 years ago and has extremity (acral) ulcers. However, the ulcers relapsed and there was response to Bosentan therapy. A similar outcome was also seen at the end of the treatment periods of 4 patients from the same group. Experts concluded that MSCs are successful in improving acral ulcer and second-degree skin thickening, but further studies are needed to achieve a conclusion in heterogenic clinical symptoms.  Later, minor studies have also shown that local injection of adipose tissue-derived MSC into the face and fingers showed positive outcomes in the treatment of systemic sclerosis patients with autologous blood and bone marrow-derived mononuclear blood cells and autologous bone marrow-derived MSC applications. No remarkable toxic affect is noted in any of these studies. 

Primary Sjögren's Syndrome 

Significant results were obtained in the umbilical cord-derived MSC treatment performed on 24 patients with severe Sjögren’s syndrome by a center. Improvement is noted in SICCA symptoms, severe systemic involvements, autoantibody levels and saliva flow in most of the patients. Moreover, no toxic affect is noted. Considering these positive results, an increase in the number of prospective and controlled clinical studies can be expected in order to obtain new information on Sjögren's syndrome treatment with MSC.

Systemic Lupus Erythematosus (SLE) 

Since 2010, changes in the course of the diseases of more than 300 treatment-resistant SLE patients (most of them from a single center) after MSC treatments have been published. MSCs obtained from different sources, including autologous or allogenic bone marrow and allogenic umbilical cord-derived, were used in most of these treatments. Positive results were obtained in most of the patients, while some of them showed increase in circulation-regulatory T cell count, despite no improvement was seen in the symptoms. Considering all these studies, experts conclude that MSCs are safe and applicable for treatment-resistant SLE patients; however, the results of randomized, controlled, prospective studies from more centers should also be evaluated to prove these inferences

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