Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells： Mediated Restoration of Endometrial Receptivity and Their Potential to Improve IVF–ET Outcomes

Background: Intrauterine adhesion (IUA), a fibrotic disorder characterized by endometrial basal layer damage, severely impairs endometrial receptivity and fertility. Conventional hysteroscopic adhesiolysis restores uterine morphology but fails to reverse fibrosis or promote functional regeneration. Human umbilical cord mesenchymal stem cell–derived exosomes (UCMSCs-EXOs) have emerged as a promising acellular therapeutic strategy due to their potent regenerative and anti-fibrotic properties. This study aimed to evaluate the therapeutic potential of UCMSCs-EXOs in restoring endometrial receptivity in a rat model of IUA. Methods and Results: UC-MSCs were isolated from Wharton’s jelly, characterized by flow cytometry and trilineage differentiation, and their exosomes were purified via ultracentrifugation and confirmed by TEM, DLS, and Western blotting for CD9, CD63, and TSG101. A mechanical injury model of IUA was established in female Sprague–Dawley rats (n = 24), which were divided into control, model, UC-MSCs, and UCMSCs-EXOs groups. One week post-injury, intrauterine administration of UCMSCs-EXOs markedly enhanced endometrial regeneration. Compared with the model group, UCMSCs-EXOs treatment significantly increased endometrial thickness (0.40 ± 0.02 mm vs. 0.10 ± 0.04 mm), gland count (28.18 ± 3.18 vs. 16.56 ± 2.32), and reduced collagen deposition (13.49 ± 1.15% vs. 30.62 ± 4.44%). Immunohistochemistry further revealed upregulated cytokeratin expression, indicating enhanced epithelial proliferation. Conclusions: UCMSCs-EXOs effectively restore endometrial structure and function by promoting epithelial proliferation and inhibiting fibrosis, demonstrating therapeutic efficacy comparable to their parent cells. As a cell-free alternative, UCMSCs-EXOs present a novel and promising strategy for IUA treatment, with the potential to improve IVF-ET outcomes.