Human menstrual blood-derived mesenchymal stem cells regulation of the EGF/Ras p21 pathway as a potential therapeutic target for thin endometrium

Human infertility is caused by many factors, among which thin endometrium is the main reason for poor embryo implantation. Currently, stem cell therapy could be a potential approach in treating human endometrial disorder like thin endometrium. In this study, we aimed to explore the influence of menstrual stem cells from non-thin endometrium (NTE-MenSCs) and thin endometrium (TE-MenSCs) on the phenotype of endometrial epithelial cells (EECs). The MenSCs were isolated from women with and without thin endometria, characterized and co-cultured with the EECs. The expression of cytokeratin 7 (CK7) was verified by immunofluorescence while the detection stem cell markers was determined flow cytometry. Osteogenic and adipogenic differentiation were induced in appropriate media. The quantitative real-time PCR and western blotting were respectively used for detecting the mRNA and protein expression levels, respectively. The CCK-8 assay was used for cell viability analysis whereas ELISA was used for the detection of cytokine levels. The results showed that the co-culture of NTE-MenSCs or TE-MenSCs and EECs promoted the proliferation, migration, and angiogenesis of endothelial progenitor cells differently. Furthermore, the TE-MenSCs promoted the expression of inflammation, vascularized adipose, and extracellular matrix related proteins. The epidermal growth factor (EGF)/Ras p21 pathway was found to mediate the influence of MenSCs on EECs. These findings are vital in that they may promote stem cell therapy of thin endometrium and enable embryo implantation in humans with thin endometrium.