Exosome-shuttled miR-7162-3p from human umbilical cord derived mesenchymal stem cells repair endometrial stromal cell injury by restricting APOL6.

Recent studies have shown that exosomes (Exos) derived from stem cells can be used as paracrine factors to regenerate cells and tissues via shuttling miRNAs. Exos derived from human umbilical cord derived mesenchymal stem cells (UCMSCs) have been found to alleviate mifepristone-induced endometrial stromal cell (ESC) injury in vitro. Information on the functions and mechanisms of Exos from UCMSC-induced endometrial repair is limited and requires more study. UCMSC-Exos were isolated and identified by Transmission Electron Microscopy, Nanoparticle Tracking Analysis software, and western blot assays. The damaged-ESC model and the UCMSC co-culture system were established, while GW4869, a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor, was used to investigate the effects of UCMSC-Exos on mifepristone-induced ESC injury. Cell apoptosis of damaged ESCs treated with UCMSCs was detected using the TUNEL assay and flow cytometry analysis. Then, miRNA microarrays were performed to detect differentially expressed miRNA profiles in both UCMSCs and ESCs after co-culturing. A subset of upregulated miRNAs was validated by qRT-PCR, and miRNA mimics/inhibitor were used to investigate the functions of miR-7162-3p. The miRNA-mRNA interactions were predicted by Targetscan software, while the miRNA binding sites were predicted by miRcode software. Moreover, dual-luciferase reporter, western blot assays and qPCR were conducted to identify the regulatory mechanisms between miR-7162-3p and APOL6. UCMSCs attenuated mifepristone-induced endometrial stromal cell apoptosis by Exos, while three miRNAs (miR-6831-5p, miR-4669, and miR-7162-3p) were both upregulated in UCMSCs and ESCs after co-culture, and were candidate effectors of UCMSC-Exos-mediated endometrial repair. We showed that miR-7162-3p was shuttled by Exos from UCMSCs and regulated the expression of APOL6 by targeting its 3'-UTR in ESCs. These results showed UCMSC-Exos protected ESCs from mifepristone-induced apoptosis and played an active role in repairing the damaged ESCs by in vitro shuttling of miR-7162-3p. The miR-7162-3p-overexpressed UCMSC-Exos may therefore be used in cell-free therapy of endometrial injury.

Shi Q ，Wang D ，Ding X ，Yang X ，Zhang Y ... -  《-》

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Proliferation of Allogeneic Endometrial Stromal Cells.

Lv CX ，Duan H ，Wang S ，Gan L ，Xu Q ... -  《-》

Exosomes Derived from Mesenchymal Stem Cells Increase the Viability of Damaged Endometrial Cells via the miR-99b-5p/PCSK9 Axis.

Li L ，An J ，Wang Y ，Liu L ，Wang Y ，Zhang X ... -  《-》

MiR-455-5p upregulation in umbilical cord mesenchymal stem cells attenuates endometrial injury and promotes repair of damaged endometrium via Janus kinase/signal transducer and activator of transcription 3 signaling.

Sun D ，Jiang Z ，Chen Y ，Shang D ，Miao P ，Gao J ... -  《-》

Umbilical cord mesenchymal stem cell-derived exosomes reverse endometrial fibrosis by the miR-145-5p/ZEB2 axis in intrauterine adhesions.

What is the specific mechanism of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exos) in regulating endometrial repair and regeneration? In this study, UCMSC-exos were harvested by differential ultracentrifugation from umbilical cord mesenchymal stem cell culture supernatant and identified with western blotting, transmission electron microscopy and nanoparticle tracking analysis. Transforming growth factor-β1 (TGFβ1) at different concentrations was used to construct the intrauterine adhesions cell model. The fibrotic markers were assessed by quantitative reverse transcription-polymerase chain reaction and western blotting. The effects of miR-145-5p over-expression on endometrial fibrosis were assessed. Dual luciferase assay was performed to verify the relationship between miR-145-5p and zinc finger E-box binding homeobox 2 (ZEB2). The isolated UCMSC-exos had a typical cup-shaped morphology, expressed the specific exosomal markers Alix, CD63 and TSG101, and were approximately 50-150 nm in diameter. TGFβ1 at 10 ng/ml significantly promoted endometrial fibrosis, which was reversed by 20 µg/ml UCMSC-exos. Exosomal miR-145-5p ameliorated TGFβ1-induced endometrial fibrosis. ZEB2 was inversely regulated by exosomal miR-145-5p as a direct target. UCMSC-exos might reverse endometrial stromal cell fibrosis by regulating the miR-145-5p/ZEB2 axis, representing a potential novel strategy to promote endometrial repair.

Li X ，Duan H ，Wang S ，Lv CX ... -  《-》