BMMSC-sEV-derived miR-328a-3p promotes ECM remodeling of damaged urethral sphincters via the Sirt7/TGFβ signaling pathway.

Stem Cell Research & Therapy
Hanke ZhangYing Gao

Abstract

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...Continue Reading

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Methods Mentioned

BETA
flow cytometry
transmission electron microscopy
protein assay
transfection
Fluorescence

Software Mentioned

ImageJ
NDP
R package
Prism
miRanda
R
view

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