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BACKGROUND

News — Thin endometrium, leading cause of recurrent implantation failure and infertility, has been found to respond to exosomes.

AIM

To investigate the efficacy of exosomes in addressing the issue of thin endometrium.

METHODS

RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs (miRNAs) in human umbilical cord mesenchymal stem cell (hucMSC) treated with exosomes enriched with endometrial cell-derived components. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways, molecular functions, and cellular components. Transwell and wound healing assays were performed to assess migratory potential, and western blotting was detected protein level.

RESULTS

A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components, comprising 27 upregulated and 26 downregulated miRNAs, which includes miR-137-3p. Enhanced migratory potential was observed in the Transwell and wound healing assays, and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3. These effects were attributed to the upregulation of miR-137-3p.

CONCLUSION

miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway, enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.

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Core Tip: This study uncovers that under hypoxic conditions, exosomal miR-137-3p, by targeting ubiquitin protein ligase E3C, activates signal transducer and activator of transcription 3, thereby enhancing the migration and differentiation of human umbilical cord mesenchymal stem cells (hucMSCs) into endometrial epithelial cells. Through microRNA sequencing and reverse transcription-quantitative polymerase chain reaction validation, it was observed that miR-137-3p is significantly upregulated in hucMSCs when co-cultured with endometrial epithelial cells. Additionally, exosome-based therapeutic system was established to evaluate the role of hucMSCs overexpressing miR-137-3p in therapeutic applications. This discovery offers novel insights into cell therapy under hypoxic environments.

• Citation: Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359
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