Department of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
J Cell Mol Med. 2024 Jun;28(12):e18451. doi: 10.1111/jcmm.18451.
Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.
骨髓间充质干细胞(BMSC)来源的外泌体可缓解大鼠盆底功能障碍(PFD)的症状。然而,肿瘤坏死因子(TNF)-α处理的BMSC 来源的外泌体对大鼠 PFD 症状的潜在治疗作用尚不清楚。用或不用 TNF-α处理的 BMSC 提取的外泌体用于治疗 PFD 大鼠。我们的研究结果显示,与对照组相比,盆腔器官脱垂(POP)患者的阴道壁组织中白细胞介素(IL)-6 和肿瘤坏死因子(TNF)-α以及基质金属蛋白酶-2(MMP2)水平显著升高。每日给予 BMSC 来源的外泌体(Exo 和 TNF-Exo)治疗,可增加 PFD 大鼠的尿量和膀胱排空压,降低最大膀胱压和漏点压。值得注意的是,与 Exo 治疗相比,TNF-Exo 治疗在恢复尿量、膀胱排空压和上述参数方面显示出更好的疗效。重要的是,TNF-Exo 在恢复 PFD 大鼠前阴道壁中多种蛋白(弹性蛋白、I 型胶原、III 型胶原、IL-6、TNF-α和 MMP2)水平方面的作用强于 Exo。用 TNF-α处理的 BMSC 来源的外泌体的应用有望成为治疗 PFD 的一种新的治疗方法。