交联透明质酸包裹的月经血源性子宫内膜干细胞对宫腔粘连的增强改善作用
Enhanced Improvement of Menstrual Blood Derived Endometrial Stem Cells Encapsulated in Cross-Linked Hyaluronic Acid on Intrauterine Adhesions.
作者信息
Pan Ying, Chang Mengyuan, Zhang Wenqiang, Zhang Shenghui, Chang Pin, Cheng Hongbin, Gao Xiao, Fan Wenqiang, Wang Wenxiang, Liu Yanli, Lin Juntang
机构信息
Stem Cell and Biotherapy Technology Research Center, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, China.
The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
出版信息
Reprod Sci. 2025 Jul 8. doi: 10.1007/s43032-025-01928-1.
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.
宫腔粘连(IUA)以宫腔内纤维性粘连为特征,常导致育龄期女性月经不调、反复流产、继发性不孕及妊娠风险增加。遗憾的是,传统临床干预措施主要包括手术分离和物理隔离,在促进受损子宫内膜再生方面疗效有限,且复发率高。因此,迫切需要研究针对IUA患者修复受损子宫内膜的新疗法,尤其是对有生育需求的患者。近年来,基于干细胞的疗法因其卓越的旁分泌作用和免疫调节功能展现出前景,成为组织再生和抗纤维化治疗的新选择。在此,我们首先证实了月经血源性子宫内膜干细胞(MenSCs)与基于透明质酸的支架XLHA联合时具有优异的生物相容性。XLHA提供的三维微环境增强了MenSCs的免疫调节作用,并延长了它们在IUA小鼠宫腔内的留存时间。随后,与单独的MenSCs或XLHA相比,封装在XLHA中的MenSCs显示出显著改善的治疗效果。这种方法不仅促进了子宫内膜形态的恢复,增加了子宫内膜腺体数量,还改善了IUA小鼠子宫内膜的凋亡和炎症。此外,封装在XLHA中的MenSCs移植显著改善了生育结局,这可能是由于IUA小鼠子宫内膜容受性得到了改善。总之,本研究证实了封装在XLHA中的MenSCs移植能有效改善IUA小鼠的子宫内膜损伤,同时阐明了其中潜在的机制。该研究为提高MenSCs在IUA治疗中的疗效提供了一种实用且经济高效的递送策略。