Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Stem Cell Res Ther. 2020 Jul 16;11(1):286. doi: 10.1186/s13287-020-01808-2.
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.
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.
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.
BMMSC-sEV promote ECM remodeling of damaged urethral sphincters by transferring miR-328a-3p to regulate the Sirt7/TGF-β1 signaling pathway.
压力性尿失禁（SUI）是一种常见且令人困扰的疾病。在保守治疗失败后，总会考虑进行侵入性手术，但术后并发症和长期复发率都很高。因此，仍需要新的治疗策略。近年来，骨髓间充质干细胞（BMMSC）在治疗 SUI 方面显示出巨大的潜力。BMMSC 对 SUI 的治疗作用主要通过旁分泌途径信号分子实现，如小细胞外囊泡（sEV）。sEV 被认为是细胞间通讯的重要介质。然而，BMMSC 衍生的 sEV 在 SUI 中的治疗效果和详细机制仍在很大程度上尚未被探索。
在体外和体内评估了 BMMSC-sEV 对细胞外基质（ECM）代谢的影响。在 SUI 大鼠模型中，检查了 TGF-β1 信号是否在有无 BMMSC-sEV 刺激的情况下被激活。对 sEV miRNAs 进行了深度测序，并评估了最有可能作为 TGF-β1 信号通路介质的 miRNAs。
BMMSC-sEV 增强了 ECM 成分（包括弹性蛋白、I 型胶原和 III 型胶原）的合成，并改善了尿道功能。此外，BMMSC-sEV 在原代成纤维细胞和大鼠尿道中激活了 TGF-β1 信号。在 BMMSC-sEV 中鉴定出了几个差异表达的 miRNAs。生物信息学分析和体外研究表明，BMMSC-sEV 中的 miR-328a-3p 可以从 BMMSC 转移到成纤维细胞，并可以调节 Sirt7/TGF-β1 信号通路。
BMMSC-sEV 通过转移 miR-328a-3p 来调节 Sirt7/TGF-β1 信号通路，促进受损尿道括约肌的 ECM 重塑。
