Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
Stem Cell Res Ther. 2019 Mar 8;10(1):80. doi: 10.1186/s13287-019-1182-4.
Previous studies revealed that urine-derived stem cells (USCs) could promote myogenesis after the impairment of the sphincter muscles. However, the effects of exosomes secreted by USCs (USCs-Exo) were not elucidated. Exosomes are nanosized membrane vesicles secreted by the cells. They have been proved to be effective in protecting against tissue injury and therapeutic in tissue repair. USCs are ideal sources of exosomes because of the noninvasive obtaining method and self-renewal abilitiy. This study aimed to show the therapeutic effects of USCs-Exo on improving stress urinary incontinence (SUI).
Rat SUI models were established in this study using vaginal balloon inflation, and urodynamic and histological examination were carried out after exosome application. The proliferation and differentiation of muscle satellite cells (SCs) were evaluated using EdU, Cell Counting Kit 8, immunofluorescence staining, and Western blot analysis. mRNAs and proteins related to the activation of SCs were detected by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.
After exosome injection, the urodynamic parameters significantly improved and the injured muscle tissue recovered well. The activation, proliferation, and differentiation of SCs were promoted. The phosphorylation of extracellular-regulated protein kinases (ERK) was enhanced. When ERK was inhibited, the promoting effect of USCs-Exo treatment disappeared.
The findings of this study elucidated the functional roles of USCs-Exo in satellite cell ERK phosphorylation and identified a novel agent for skeletal muscle regeneration, providing a basis for further exploring a cell-free correction for SUI.
先前的研究表明，尿源性干细胞（USCs）可促进括约肌损伤后的肌生成。然而，USCs 分泌的外泌体（USCs-Exo）的作用尚未阐明。外泌体是细胞分泌的纳米大小的膜囊泡。它们已被证明在防止组织损伤和组织修复方面具有治疗作用。USCs 是外泌体的理想来源，因为其具有非侵入性的获取方法和自我更新能力。本研究旨在展示 USCs-Exo 在改善压力性尿失禁（SUI）方面的治疗效果。
本研究通过阴道球囊充气建立大鼠 SUI 模型，并在应用外泌体后进行尿动力学和组织学检查。使用 EdU、细胞计数试剂盒 8、免疫荧光染色和 Western blot 分析评估肌肉卫星细胞（SCs）的增殖和分化。通过逆转录定量聚合酶链反应（RT-qPCR）和 Western blot 分析检测与 SCs 激活相关的 mRNAs 和蛋白质。
外泌体注射后，尿动力学参数显著改善，受损肌肉组织恢复良好。促进了 SCs 的激活、增殖和分化。细胞外调节蛋白激酶（ERK）的磷酸化增强。当 ERK 被抑制时，USCs-Exo 处理的促进作用消失。
本研究阐明了 USCs-Exo 在卫星细胞 ERK 磷酸化中的功能作用，并鉴定了一种用于骨骼肌再生的新型药物，为进一步探索用于 SUI 的无细胞矫正方法提供了依据。
