Li Qing, Song Jinzhong, Liu Tingting, Niu Zhong, Lu Xiufang, Jia Junhong, Wang Bingjie, Hu Binghui, Ma Wanli, Wang Xiangsheng, Han Dongfeng, Li Hua, Su Dan
Department of Anorectal Surgery, Xingtai People's Hospital, Xingtai, China.
Department of Colorectal Medicine, Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
Int J Stem Cells. 2021 Oct 31. doi: 10.15283/ijsc21065.
To evaluate the effect of exosomes (Exos) derived from silent mating type information regulation 2 homolog 1 (SIRT1)-overexpressing human bone marrow mesenchymal stem cells (BMSCs) on the recovery of pubococcygeus muscle Injury.
Exos isolated from SIRT1-overexpressing BMSCs (SIRT1/exos) were injected into a vaginal dilation-induced rat model of Stress urinary incontinence (SUI). The efficacy of Exos treatment on SUI was evaluated by determining the values of urodynamic parameters. The proliferation and differentiation of satellite cells (SCs) were examined by CCK-8 assay, Western blotting, and immunofluorescence staining. The mRNA and protein expression of molecules related to SC differentiation were detected by RT-qPCR and Western blotting, respectively. Treatment with SIRT1/exos significantly improved the values of abdominal leak point pressure (ALPP), maximum bladder volume (MBV), and estimated marginal mean in rats of SUI. Exposure of SIRT1/exos enhanced the proliferation, differentiation, and activation of SCs. Moreover, SIRT1/exos exhibited their positive effect on BMSCs by activating the ERK signaling.
Our findings demonstrated that SIRT1/exos meliorated pubococcygeus muscle injury in rats by promoting ERK pathway, which may provide a novel cell-free therapeutic strategy for SUI.
评估源自过表达沉默信息调节因子2同源物1（SIRT1）的人骨髓间充质干细胞（BMSCs）的外泌体（Exos）对耻骨尾骨肌损伤恢复的影响。
将从过表达SIRT1的BMSCs分离出的外泌体（SIRT1/exos）注射到阴道扩张诱导的压力性尿失禁（SUI）大鼠模型中。通过测定尿动力学参数值来评估外泌体治疗SUI的疗效。通过CCK-8法、蛋白质印迹法和免疫荧光染色检测卫星细胞（SCs）的增殖和分化。分别通过RT-qPCR和蛋白质印迹法检测与SCs分化相关分子的mRNA和蛋白质表达。用SIRT1/exos治疗显著改善了SUI大鼠的腹压漏尿点压力（ALPP）、最大膀胱容量（MBV）和估计边际均值。SIRT1/exos的暴露增强了SCs的增殖、分化和激活。此外，SIRT1/exos通过激活ERK信号通路对BMSCs发挥积极作用。
我们的研究结果表明，SIRT1/exos通过促进ERK途径改善大鼠耻骨尾骨肌损伤，这可能为SUI提供一种新的无细胞治疗策略。
