Use of extracellular vesicles as a therapeutic option for graft-versus-host disease: systematic review of in vivo studies

The use of extracellular vesicles (EVs) can be a therapeutic option for pathologies involving immunological mechanisms, including graft-versus-host disease (GVHD). This study evaluated, through a systematic review, the applicability of EVs for therapy of GVHD. The study was conducted based on the recommendations of PRISMA to answer the PICO question: "In animal models of GVHD, what is the effect of EVs therapy compared to non-use of EVs?" Thus, systematic research was performed in the different databases up to May 2025. Control of GVHD and the molecular mechanisms involved were considered the primary and secondary outcomes, respectively. The risk of bias in the selected studies was assessed using SYRCLE's RoB tool. A total of 3468 articles were analyzed, and after applying eligibility criteria, 14 studies were included. The studies demonstrated EVs controlled development of GVHD with reduction of tissue inflammatory processes, suppression of cellular apoptosis, an increase in survival rates, and attenuation of damage, particularly in the skin, liver, and intestines. An increase in anti-inflammatory cytokines and regulatory T cells, and a decrease in inflammatory cytokines and activation of Th1 and Th17 lymphocytes was noted following EV administration. EVs were associated with the control of GVHD in animal models; however, further studies on optimal cell source and dosage, as well as safety and efficacy, are needed before clinical application.