Abstract
BackgroundPrevious 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).MethodsRat 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.ResultsAfter 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.ConclusionThe 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.
Highlights
Previous studies revealed that urine-derived stem cells (USCs) could promote myogenesis after the impairment of the sphincter muscles
USCs were confirmed with a fibroblast-like morphology using light microscopy (Fig. 1A)
flow cytometry (FCM) analysis demonstrated that USCs were positive for CD29, CD73, CD90, and CD44 antigen and negative for CD34, CD45, and human leukocyte antigen DR (HLA-DR) (Fig. 1B)
Summary
Previous studies revealed that urine-derived stem cells (USCs) could promote myogenesis after the impairment of the sphincter muscles. 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. This study aimed to show the therapeutic effects of USCs-Exo on improving stress urinary incontinence (SUI). Urine-derived stem cells (USCs) can be obtained by noninvasive methods and are easy to culture and proliferate, which makes them an ideal source for exosome extraction [16, 17]. Our previous studies demonstrated that exosomes secreted by urine-derived stem cells (USCs-Exo) could promote wound healing and bone regeneration [18, 19]. USCs-Exo could enhance the phosphorylation of ERK and promote the activation, proliferation, and differentiation of satellite cells (SCs), thereby promoting the recovery of the damaged pubococcygeus muscle and improving the symptoms of SUI
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