Background: Stress urinary incontinence (SUI) is a common and bothersome condition. Invasive surgery will always be considered after conservative treatment fails, but the rates of postoperative complications and long-term recurrence are high. Thus, a new treatment strategy is still needed. In recent years, bone marrow mesenchymal stem cells (BMMSC) have shown great promise for SUI treatment. The therapeutic effects of BMMSC on SUI are achieved mainly by paracrine pathway signaling molecules, such as small extracellular vesicles (sEV). sEV are recognized as essential mediators of cell-to-cell communication. However, the therapeutic effects and detailed mechanisms of BMMSC-derived sEV in SUI remain mostly unexplored. Methods: The effects of BMMSC-sEV on extracellular matrix (ECM) metabolism were assessed in vitro and in vivo. In a SUI rat model, TGF-β1 signaling was examined with or without BMMSC-sEV stimulation. sEV miRNAs were deeply sequenced, and the most likely miRNAs were evaluated as mediators of the TGF-β1 signaling pathway. Results: BMMSC-sEV enhanced the synthesis of ECM components, including elastin, collagen I, and collagen III, and improved urethral function. Furthermore, BMMSC-sEV activated TGF-β1 signaling in primary fibroblast cells and in rat urethras. Several differentially expressed miRNAs were identified in the BMMSC-sEV. Bioinformatics analysis and in vitro studies showed that BMMSC-sEV miR-328a-3p can be transferred from BMMSC to fibroblasts and can regulate the Sirt7/TGF-β1 signaling pathway. Conclusion: BMMSC-sEV promote ECM remodeling of damaged urethral sphincters by transferring miR-328a-3p to regulate the Sirt7/TGF-β1 signaling pathway.
Exosomes, small extracellular vesicles with diameters of 40-100nm, are generated through the fusion of multivessel with plasma membrane and secreted by a variety of living cells. Exosomes contain lipid bilayer membrane and releasable functionally active proteins, mRNA and microRNAs (miRNAs). This article reviews the latest progress of researches on exosomes in diseases that lead to infertility.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.