3D HucMSCs衍生的细胞外囊泡通过BECN1递送增强了治疗宫腔粘连的疗效
3D HucMSCs derived extracellular vesicles enhanced therapeutic efficacy in treating intrauterine adhesions via BECN1 delivery.
摘要(中文译文)
宫腔粘连（IUA）是导致女性不孕的重要原因，也是育龄期女性面临的重大公共卫生问题。新近证据凸显了间充质干细胞来源的细胞外囊泡（EVs）在宫腔粘连治疗中的治疗潜力。然而，传统的二维（2D）培养体系限制了EVs的产量和生物学活性。本研究采用基于甲基丙烯酰化明胶（GelMA）微球的三维（3D）培养平台培养人脐带间充质干细胞并分离间充质干细胞来源的细胞外囊泡（MSC-EVs）。对比分析表明，与2D-EVs相比，3D-EVs在恢复米非司酮损伤的人子宫内膜基质细胞（hESCs）的增殖、迁移、活力以及减轻纤维化方面表现出显著更优的治疗效果。在宫腔粘连动物模型中，GelMA包裹的3D-EVs治疗展现出显著的组织再生能力。该治疗有效改善了子宫内膜结构，包括黏膜厚度和腺体密度，减轻了子宫内膜纤维化，并最终改善了生殖结局。蛋白质组学分析和功能验证实验的结果显示，3D-EVs中BECN1表达升高有助于增强3D-EVs对损伤hESCs的治疗效果。本研究确立了3D培养来源的EVs作为一种创新的无细胞治疗策略用于子宫内膜再生，既解决了传统EVs生产方法的局限性，也满足了临床对有效宫腔粘连治疗的需求。我们的研究结果为针对子宫内膜病变的先进再生策略奠定了基础。
Abstract
Intrauterine adhesion (IUA) is a significant cause of female infertility and a critical public health concern among women of childbearing age. Emerging evidence has highlighted the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (EVs) in IUA treatment. However, conventional two-dimensional (2D) culture systems impose constraints on the yield and biological activity of EVs. In this study, we employed a three-dimensional (3D) culture platform based on gelatin methacrylate (GelMA) microspheres to culture human umbilical cord mesenchymal stem cells and isolate MSC-EVs. Comparative analysis demonstrated that 3D-EVs exhibited significantly superior therapeutic effects on restoring the proliferation, migration, viability, and alleviating fibrosis of mifepristone-injured human endometrial stromal cells (hESCs) compared with 2D-EVs . In IUA animal models, treatment with GelMA-encapsulated 3D-EVs exhibited remarkable regenerative capabilities. The treatment effectively rejuvenated endometrial structure including mucosal thickness and glandular density, ameliorated endometrial fibrosis, and ultimately improved reproductive outcomes. Results from proteomic profiling and functional verification assays revealed that elevated expression of BECN1 in 3D-EVs contributes to the enhanced therapeutic effect of 3D-EVs on injured hESCs. This study establishes 3D culture-derived EVs as an innovative cell-free therapeutic approach for endometrial regeneration, addressing both the limitations of traditional EVs production methods and the clinical need for effective IUA treatments. Our findings provide a foundation for advanced regenerative strategies targeting endometrial pathologies.
如何引用
AMA
Juan Peng, Juan Zhang, Qingzhao Li, Weijun Liu, Wenda Zou, Liyu Zhu, et al. 3D HucMSCs derived extracellular vesicles enhanced therapeutic efficacy in treating intrauterine adhesions via BECN1 delivery.. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103276.
APA
Juan Peng, Juan Zhang, Qingzhao Li, Weijun Liu, Wenda Zou, Liyu Zhu, et al (2026). 3D HucMSCs derived extracellular vesicles enhanced therapeutic efficacy in treating intrauterine adhesions via BECN1 delivery.. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103276
GB/T 7714
Juan Peng, Juan Zhang, Qingzhao Li, Weijun Liu, Wenda Zou, Liyu Zhu, et al. 3D HucMSCs derived extracellular vesicles enhanced therapeutic efficacy in treating intrauterine adhesions via BECN1 delivery.[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103276.
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