温敏水凝胶作为间充质干细胞来源细胞外囊泡的缓释载体在宫腔粘连治疗中的应用。

Thermosensitive hydrogel as a sustained release carrier for mesenchymal stem cell-derived extracellular vesicles in the treatment of intrauterine adhesion.

机构信息

Department of Obstetrics and Gynecology, Reproductive Medicine Center, First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui, 230022, China.

NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui, 230032, China.

出版信息

J Nanobiotechnology. 2024 Sep 17;22(1):570. doi: 10.1186/s12951-024-02780-2.

Abstract

Intrauterine adhesion (IUA), a prevalent etiology of female infertility, is attributed to endometrial damage. However, conventional therapeutic interventions for IUA are plagued by high recurrence rates. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) demonstrate the promising therapeutic effects on IUA, but the current efficacy of extracellular vesicles (EVs) is hindered by lower retention and bioavailability. In this study, a thermosensitive hydrogel was utilized as a prolonged release carrier to improve the retention and bioavailability of hUCMSC-EVs in IUA treatment. The hydrogel-EVs complex effectively prolonged EVs retention in human endometrial stromal cells and an IUA mouse model. The complex exhibited superior protection against cellular injury, significantly alleviated endometrial damage, inhibited fibrosis, suppressed inflammation, and improved fertility compared to EVs alone. The results indicated that thermosensitive hydrogel enhanced the therapeutic capacity of EVs for IUA by prolonging their retention in the uterine environment. The hydrogel-EVs complex provides a novel strategy for the sustained release of hUCMSC-EVs in the treatment of IUA.

摘要

宫腔粘连(IUA)是女性不孕的常见病因,其发病机制与子宫内膜损伤有关。然而,IUA 的传统治疗方法存在较高的复发率。人脐带间充质干细胞来源的细胞外囊泡(hUCMSC-EVs)在治疗 IUA 方面表现出良好的治疗效果,但目前细胞外囊泡(EVs)的疗效受到保留率和生物利用度低的限制。在本研究中,我们使用温敏水凝胶作为延长释放载体,以提高 hUCMSC-EVs 在 IUA 治疗中的保留率和生物利用度。水凝胶-EVs 复合物可有效延长 EVs 在人子宫内膜基质细胞和 IUA 小鼠模型中的保留时间。与单独使用 EVs 相比,该复合物对细胞损伤具有更好的保护作用,显著减轻了子宫内膜损伤,抑制了纤维化、炎症反应,并提高了生育能力。结果表明,温敏水凝胶通过延长 EVs 在子宫环境中的保留时间,增强了 EVs 治疗 IUA 的治疗能力。水凝胶-EVs 复合物为 hUCMSC-EVs 在 IUA 治疗中的持续释放提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a7/11406736/aff25b258e74/12951_2024_2780_Fig1_HTML.jpg

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