Potential role of extracellular vesicles from different sources in unexplained recurrent pregnancy loss†

Unexplained recurrent pregnancy loss (URPL) is complex and has unknown etiologies, simultaneously endangering the patient's physical and mental health. Despite significant advancements in shifting from conventional treatments to cell therapy, clinical research and application in cell therapy have been constrained by its immunogenic properties and biosafety. As a new cell-cell communication pathway, extracellular vesicles (EVs) can transfer their bioactive cargos to other cells by endocytosis, ligand-receptor engagement, or direct fusion, thereby executing diverse biological functions both in proximity and across great distances. It is noteworthy that the role of EVs as a cell-free therapy in the form of a drug transporter has garnered increased attention, and some studies have demonstrated EVs involvement in the key pathology of URPL. This review methodically summarizes the functions of EVs from various sources in URPL, including mesenchymal stem cells, placenta, and other sources of EVs. Furthermore, we discuss the significance of EVs as possible diagnostic biomarkers and therapeutic strategies for URPL and the key questions that need to be addressed in future research.