Exosomes secreted by adipose-derived mesenchymal stem cells regulate type I collagen metabolism in fibroblasts from women with stress urinary incontinence

Background: Mesenchymal 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). Methods: Periurethral 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. Results: The 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 collal 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 collal 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. Conclusions: adMSC-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.