Mesenchymal stromal cell-derived extracellular vesicles for intrauterine adhesions: from cargo and mechanism to product standardization and local delivery

Background Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are being developed as cell-free regenerative products for intrauterine adhesions (IUA), but the translational literature is limited by inconsistent terminology, heterogeneous products, and predominantly rodent evidence. Main body This review integrates the inflammation-fibrosis circuit of IUA with reported MSC-EV cargo-target pairs, including galectin-1/JAK-STAT, miR-202-3p/MMP11, miR-543/N-cadherin, UBR4/YAP, and miR-340-3p/METTL3-HMOX1. It distinguishes direct uterine evidence from mechanistic extrapolation, discusses parent-cell source and culture effects, and evaluates collagen scaffolds, decellularized matrices, and injectable hydrogels as local delivery systems. Recent pooled animal evidence supports improvements in endometrial thickness, gland number, fibrosis, and embryo-related outcomes, but pregnancy-rate evidence remains uncertain. MISEV2023-aligned characterization, mechanism-linked potency assays, standardized dose metrics, biodistribution, and reproductive toxicology are essential before efficacy can be interpreted across studies. The trial landscape has also changed: an IUA-specific study of intrauterine hUCMSC-EV administration was registered in 2026, although peer-reviewed clinical efficacy data remain unavailable. Mechanistic claims are graded by whether primary experiments provide cargo perturbation, direct target validation, and functional rescue, while hydrogel performance is considered in relation to vesicle integrity, phase-matched release, and uterine retention. Conclusion MSC-EVs have a coherent preclinical rationale for IUA, particularly when coupled to local retention systems. EV–hydrogel therapy remains investigational and may have combination-product regulatory features depending on product design and jurisdiction; it is not an established fertility treatment. Progress requires reproducible manufacturing, defined potency, stage-gated safety evaluation, and trials centered on adhesion recurrence, menstrual recovery, live birth, and obstetric safety. Structural recovery is treated as a surrogate outcome rather than evidence of proven reproductive benefit.