Abstract
BackgroundMesenchymal stem cells (MSC) have gained credibility as a therapeutic tool partly due to their potential to secrete factors such as cytokines and chemokines. Recently, exosomes, which mediate intercellular communication by delivering biomolecules such as mRNA and miRNA into recipient cells, have gained attention as a new and valuable therapeutic strategy in regenerative medicine. However, the potential role of exosomes secreted by adipose-derived mesenchymal stem cells (adMSC-Exos) in collagen metabolism is not well understood. The purpose of this study was to evaluate the effects of adMSC-Exos on collagen metabolism in cultured fibroblasts from women with stress urinary incontinence (SUI).MethodsPeriurethral vaginal wall tissues of postmenopausal women with or without SUI were collected during transvaginal surgical procedures. Primary fibroblasts were cultured from periurethral vaginal wall tissues, and the levels of type I collagen mRNA and protein were examined by qRT-PCR and western blotting. MSC were isolated from human adipose tissue by enzymatic digestion. Exosomes were prepared by ultracentrifugation of adMSC-conditioned medium (adMSC-CM) and were confirmed by transmission electron microscopy and western blot analyses. The effects of adMSC-CM and adMSC-Exos were assessed using qRT-PCR and western blotting.ResultsThe type I collagen content was significantly decreased in periurethral vaginal wall tissues and cultured vaginal fibroblasts from women with SUI. adMSC-CM increased the expression of the col1a1 gene in vaginal fibroblasts from women with SUI. adMSC-Exos could be successfully isolated from adMSC-CM and could be transferred to fibroblasts efficiently. adMSC-Exos increased the expression of col1a1 in vaginal fibroblasts from women with SUI, and when the fibroblasts were treated with adMSC-Exos, the expression levels of TIMP-1 and TIMP-3 in fibroblasts were upregulated, with significant downregulation of MMP-1 and MMP-2 expression levels.ConclusionsadMSC-Exos increased type I collagen contents by increasing collagen synthesis and decreasing collagen degradation in vaginal fibroblasts from women with SUI. adMSC-Exos may be a novel therapeutic approach for treating SUI.
Highlights
Mesenchymal stem cells (MSC) have gained credibility as a therapeutic tool partly due to their potential to secrete factors such as cytokines and chemokines
We found that fibroblasts from the women with Stress urinary incontinence (SUI) exhibited significant decreases in the expression levels of TIMP metallopeptidase inhibitor 1 (TIMP-1), TIMP metallopeptidase inhibitor 2 (TIMP-2) and TIMP metallopeptidase inhibitor 3 (TIMP-3), while the mRNA expression levels of matrix metallopeptidase 1 (MMP-1), Matrix metallopeptidase 2 (MMP-2), and Matrix metallopeptidase 9 (MMP-9), which reportedly increase collagen degradation in stress incontinence, were significantly increased (Fig. 1h)
When the fibroblasts were treated with adMSC-conditioned medium, we found that the expression levels of TIMP-1 and TIMP-3 were significantly
Summary
Mesenchymal stem cells (MSC) have gained credibility as a therapeutic tool partly due to their potential to secrete factors such as cytokines and chemokines. The potential role of exosomes secreted by adipose-derived mesenchymal stem cells (adMSC-Exos) in collagen metabolism is not well understood. The purpose of this study was to evaluate the effects of adMSC-Exos on collagen metabolism in cultured fibroblasts from women with stress urinary incontinence (SUI). The underlying pathology and cause of SUI remain unknown, but many studies suggest that the development of SUI in women is accompanied by fibroblast dysfunction and reduced collagen [4,5,6,7,8]. Surgical treatment is the current gold standard therapy for SUI, and short-term success has been achieved with injectable bulking agents [9, 10]. Given its ability to induce tissue regeneration, stem cell-based treatment represents a promising strategy to overcome the limitations of current treatments for SUI
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