Discussion
rheumatoid arthritis, tumor necrosis, TNF-α, toxicity, swollen joints, inflammation, UC, pain, RA
RHEUMATOID ARTHRITIS, TUMOR NECROSIS, ADVERSE EVENTS, INFLAMMATION, INFLAMMATORY DISEASE
Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments during the last decades, owing to their potential applications such as anti-inflammatory, uncommon immunomodulatory competence, self-renewal, and multipotency properties. Many ongoing clinical trials are investigating the safety and efficacy of MSCs therapies to treat inflammatory diseases, which have shown positive clinical outcomes, with improved swollen joints, pain level, and quality of life. Furthermore, few RCT or non-RCT of MSCs conducted on rheumatoid arthritis (RA) patients have also shown some positive performance without serious adverse events. In this study, we presented a summary of active RA clinical trials with MSCs therapy that included a control group (Our Systematic Review and Meta-analysis are the first work that substantially summarizes the safety of systemic MSCs administration isolated from the umbilical cord (UC), adipose tissue (AT), and bone marrow (BM) in the treatment of rheumatoid arthritis. This work did not find serious adverse events per system organ class, during or after MSCs administration, and provided initial safety and efficacy assessment for MSCs; in general, infusions of MSCs were safe and well tolerated in the included studies. Serum levels of cellular mediators that drive inflammation in RA, such as interleukin-6 and tumor necrosis factor alfa (TNF-α), decreased after the first MSCs treatment without evidence of toxicity at the dosage concentration in a period studied.Due to the great variability in evaluating the clinical efficacy between the studies included, it was impossible to perform a meta-analysis for these outcomes; however, a comprehensive summary was performed, in which the HAQ and DAS28 scores decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed. However, studies did not show improvement beyond 12 months without continuous treatment administration.Currently, the most well-known sources of MSCs are BM, AT, and UC; although MSCs can be isolated from any human tissue, there exist restrictions such as the availability of source tissues and invasiveness of the isolation procedures and different donor’s features [