Background: Multiple sclerosis (MS) typically arises in early/middle adulthood and is characterized by a progressive disability of the central nervous system (CNS). Currently approved therapies do not promote tissue repair or stop disease progression. Emerging data demonstrate that stem cells present a great potential in regenerative medicine and, consequently, have also been widely investigated as a potential treatment for MS. Therefore, the aim of this study was to conduct a systematic review to inquire into the safety, tolerability, and efficacy of mesenchymal stem cells (MSCs) therapies in MS. Methods: Three electronic databases (Web of Science, PubMed, and Cochrane) were searched from April until June 2019. Clinical trials or case reports with information related to the effects of MSC therapies in MS patients were considered for this review. Results: 10 manuscripts were selected, namely 7 uncontrolled clinical trials, 2 randomized controlled clinical trials, and 1 case report. The overall quality of the studies was considered good. Besides minor adverse events (AEs), it was reported one case of encephalopathy with seizures and two cases of iatrogenic meningitis, which were not related to the treatment, but with the administration route. The analyses of the expanded disability status scale (EDSS) in the uncontrolled clinical trials demonstrated that 48 patients improved, 39 maintained and 16 worsened their clinical condition. Regarding the randomized studies, one did not show statistically significant variations in the mean EDSS score and in the other the mean EDSS score was statistically significantly lower for the experimental group. The case report also showed an improvement in the EDSS score. Conclusions: MSCs transplantation proved to be a safe and tolerable therapy. Their potential therapeutic benefits were also validated. However, larger placebo controlled blinded clinical trials will be required to establish the long term safety and efficacy profile of these therapies for MS. Their translation into the clinical practice can provide a new hope for the patients of this highly debilitating disease.
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