Mesenchymal Stem Cells and Their Extracellular Vesicles in Preeclampsia: Mechanisms, Translational Challenges, and Therapeutic Perspectives

Abstract Preeclampsia (PE) is a life-threatening, pregnancy-specific complication characterized by systemic endothelial dysfunction and placental insufficiency; however, standard clinical management remains inadequate. Among the strategies investigated to address this limitation, the use of mesenchymal stem cell (MSC)-based therapies, particularly those utilizing MSC-derived small extracellular vesicles (sEVs), represents a promising, exploratory therapeutic approach. This narrative review synthesizes evidence regarding the therapeutic roles of perinatal tissue-derived MSCs and sEVs—including those from the umbilical cord, placenta, amnion, and decidua—in mitigating PE pathology. The evaluation focuses on critical underlying mechanisms, specifically the modulation of trophoblast behaviors, restoration of vascular homeostasis through the VEGF/sFlt-1/PlGF axis, attenuation of oxidative stress, and mediation of epigenetic regulation via ncRNAs. Furthermore, the compiled evidence is categorized across a spectrum ranging from in vitro mechanistic studies to in vivo rodent models, highlighting significant translational bottlenecks such as MSC source heterogeneity, a lack of standardized manufacturing protocols, and unresolved safety concerns regarding long-term fetal and maternal effects. By integrating these perspectives, this article outlines a roadmap for future research, emphasizing that standardized functional potency assays and rigorous early-phase clinical evaluations are necessary to advance MSC-based interventions from experimental models toward objective clinical validation.