Engineering modification of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorates polycystic ovary syndrome by enhancing the ovarian environment and regulating follicular development

作者：Ding Kang, Xinyu Wang, Wei Liu, Yating Chen, Fang-Rui Xue, Chun-Ru Song, Yishan Dong, Jun Zhai, Chengguang Liang, Jing Li · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04610-0 · 被引用次数：11 · 研究领域：Reproductive Biology and Fertility、Ovarian function and disorders、Extracellular vesicles in disease

BACKGROUND: Polycystic Ovary Syndrome (PCOS), is a complex endocrine disorder affecting 6-21% of reproductive-aged women, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Current clinical management relies on lifestyle modifications and symptom-targeted therapies due to the absence of curative interventions. In recent years, Laparoscopic ovarian drilling (LOD), a surgical procedure that induces controlled ovarian damage to stimulate primordial follicle activation and regulate follicular growth, has emerged as an established therapeutic intervention for infertility in PCOS. Beyond surgical approaches, the 740Y-P peptide-PI3K-Akt pathway agonist can achieve similar effects to LOD in enhancing follicular activation and restoring fertility. However, translating 740Y-P into clinical practice remains challenging due to systemic delivery limitations, including poor bioavailability and inadequate ovarian targeting. To address this, naturally secreted sEVs have gained attention as versatile therapeutic vectors owing to their intrinsic immunomodulatory properties and homing tendency. METHODS: In this study, We engineered HucMSC-sEVs through anchor peptide-mediated surface Connections to deliver the 740Y-P peptide. The N-terminus of 740Y-P was conjugated to the C-terminus of the CD63-binding anchor peptide, enabling exogenous loading via co-incubation (4 °C, 12h). Engineered sEVs were characterized for peptide loading efficiency and targeting ca...