Enhanced Improvement of Menstrual Blood Derived Endometrial Stem Cells Encapsulated in Cross-Linked Hyaluronic Acid on Intrauterine Adhesions.

Intrauterine adhesions (IUA), characterized by fibrotic adhesions within the uterine cavity, frequently result in menstrual irregularities, recurrent miscarriages, secondary infertility, and increased pregnancy risks among women of childbearing age. Unfortunately, conventional clinical interventions mainly including surgical separation and physical isolation exhibit limited efficacy in promoting the regeneration of the injured endometrium and are associated with a high recurrence rate. Consequently, it is imperative to investigate novel therapies aimed at repairing the injured endometrium in IUA patients, particularly those desiring fertility. Recently, stem cell-based therapies have exhibited promise due to their superior paracrine action and immunomodulation, emerging as a new alternative for tissue regeneration and anti-fibrosis treatment. Herein, we first confirmed the excellent biocompatibility of menstrual blood-derived endometrial stem cells (MenSCs) when combined with XLHA-a hyaluronic acid-based scaffold. The 3D microenvironment provided by XLHA enhanced the immunomodulation of MenSCs and prolonged their retention in uterine cavity of IUA mice. Subsequently, MenSCs encapsulated in XLHA exhibited significantly improved therapeutic outcomes compared to MenSCs or XLHA alone. This approach not only facilitated recovery of endometrial morphology and increased the number of endometrial glands but also ameliorated the apoptosis and inflammation in the endometrium of IUA mice. Furthermore, the transplantation of MenSCs encapsulated in XLHA significantly improved fertility outcomes, likely due to the improved endometrial receptivity in IUA mice. In conclusion, this study confirms that the transplantation of MenSCs encapsulated in XLHA effectively ameliorates endometrial injury in IUA mice while elucidating the potential mechanisms involved. This research provides a practical and cost-effective delivery strategy for enhancing the therapeutic efficiency of MenSCs in IUA treatment.