Human amniotic fluidic derived-extracellular vesicles enriched by miR-29 ameliorate endometrial fibrosis and promote repair of damaged endometrium in an experimental model of intrauterine adhesion.

BACKGROUND

Intrauterine adhesions (IUAs) are defined by excessive fibrotic remodeling, failure of endometrial regeneration, and impaired fertility, and that have not yet had any effective treatment options. Human amniotic fluid-derived extracellular vesicles (hAF-EVs) have inherent regenerative potential and represent a promising platform for targeted delivery of antifibrotic microRNAs such as miR-29.

METHODS

A murine IUA model was established after mechanical damage of the endometrium. Unmodified hAF-derived EVs or miR-29-enriched hAF-EVs were administered to mice. Histological and immunohistochemical methods, quantitative PCR, and fertility tests were used to determine endometrial regeneration, fibrosis, angiogenesis, and molecular fibrogenic marker expression.

RESULTS

Both hAF-EVs and miR-29-enriched hAF-EVs significantly improved endometrial architecture, reduced collagen deposition, and enhanced fertility outcomes compared with untreated IUA controls. While unmodified EVs exerted robust regenerative and antifibrotic effects, miR-29 enrichment resulted in greater suppression of TGF-β/SMAD3-associated fibrogenic signaling, enhanced angiogenesis, and selective improvement in implantation-related parameters. Multiple histological results revealed similar recovery in the two EV-treated groups.

CONCLUSION

hAF-derived EVs constitute an effective cell-free therapeutic strategy for attenuating fibrosis and promoting endometrial repair following intrauterine adhesions. Enrichment with miR-29 provides selective enhancement of molecular and functional outcomes, supporting its role as a targeted modulatory component within an EV-based regenerative platform.