CD73-Positive Small Extracellular Vesicles Derived From Umbilical Cord Mesenchymal Stem Cells Promote the Proliferation and Migration of Pediatric Urethral Smooth Muscle Cells Through Adenosine Pathway

Abstract

Smooth muscle cells (SMCs) are the main functional component of urethral tissue, but are difficult to proliferate in vitro. Mesenchymal stem cells (MSCs) and mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been shown to promote tissue repair by regulating the proliferation and migration of different types of cells. In this study, we investigated the effect of umbilical cord mesenchymal stem cell-derived sEV (UCMSC-sEV) on the proliferation and migration of pediatric urethral smooth muscle cells (PUSMCs) and the mechanism by which sEV regulates the function of PUSMCs. We observed that UCMSC-sEV can significantly promote the proliferation and migration of PUSMCs in vitro. UCMSC-sEV exerted proliferation and migration promotion effects by carrying the CD73 to PUSMCs and catalyzing the production of adenosine. Conversely, the effect of UCMSC-sEV on the proliferation and migration of PUSMCs were no longer observed with addition of the PSB12379 as a CD73 inhibitor. It was found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in PUSMCs was activated by adenosine or UCMSC-sEV intervention. In summary, UCMSC-sEV promoted proliferation and migration of PUSMCs in vitro by activating CD73/adenosine signaling axis and downstream PI3K/AKT pathway. Thus, we concluded that UCMSC-sEV may be suggested as a new solution strategy for the urethral tissue repair.

Identification and analysis of MSC-Exo-derived LncRNAs related to the regulation of EMT in hypospadias

“…Yao et al found that MSC-Exos inhibited the EMT process of endometrial epithelial cells via the TGF-β1/Smad signaling pathway, thus promoting endometrial repair [ 13 ]. Xiao et al reported that miR-23a-3p and miR-182-5p transferred by MSC-Exos inhibited the NF-κB and Hedgehog pathways by silencing Ikbkb and destabilizing IKKβ, thus reversing the EMT process in LPS-induced pulmonary injury [ 14 ].…”

CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis

“…Mesenchymal stem cell–derived small extracellular vesicles (MSC-sEVs) perform well in tissue damage repair, immune regulation, and promoting angiogenesis [ 10 , 11 ]. We have found that umbilical cord mesenchymal stem cell exosomes (UCMSC-exo) can significantly promote the proliferation and migration of pediatric urethral smooth muscle cells (PUSMCs) in vitro by delivering CD73 molecules to PUSMCs and catalyzing the production of adenosine (ADO) and that the PI3K/AKT signaling pathway in PUSMCs is activated after ADO or UCMSC-exo intervention [ 12 ]. Based on this, we hypothesized that the effect of PU-MSLCs on urethral repair may be accomplished through the proangiogenic effect of PU-MSLC-derived small extracellular vesicles (PUMSLC-sEVs) and that CD73 molecules and ADO (a CD73 metabolite) promotes angiogenesis.…”