Extracellular vesicles as therapeutic agents in rheumatoid arthritis: a systematic review of current evidence

Rheumatoid arthritis (RA) is defined as a chronic autoimmune disease that severely influences a patient's quality of life. Extracellular vesicles (EVs) have gained much attention in recent years as one of the most potent therapeutic agents for the treatment of RA. A systematic review was performed with the purpose of assessing the current evidence relating to the therapeutic applications of EVs in RA. The systematic search was performed in the databases of PubMed, Scopus, and Web of Science, from inception times to September 2024. All studies investigating the use of EVs for the treatment of RA were included. The quality appraisal of selected articles and data extraction regarding EV characteristics, therapeutic applications, and associated outcomes were performed. Of the 1418 initially identified articles, 59 studies met inclusion criteria. Regarding their cellular origins, most EVs were derived from mesenchymal stem cells, followed by immune cells. The main therapeutic mechanisms included modulation of the immune response, reduction of inflammation, and repair of tissues. Recent trends are toward increasing interest in engineered EVs and combination therapies. Indeed, most studies reported positive outcomes with regard to lowered inflammation and improved joint function. On the other hand, standardization of the metrics of evaluation considerably varied between different studies. EVs are promising therapeutic agents in the treatment of RA by modulating immune responses. Standardization, delivery systems, and clinical translation are challenges yet to be overcome. Future studies will be directed to optimize EV engineering, targeted delivery systems, and large-scale clinical trials.