Umbilical cord-derived mesenchymal stem cells combined with kaempferol synergistically promote repair of damaged endometrium by modulating JAK2/STAT3 signaling pathway.

Intrauterine adhesion (IUA) is a disease caused by endometrial damage without effective treatments. Stem cell therapy has been initiated as a new attempt to repair and regenerate injured tissues. However, the therapeutic efficacy of stem cell therapy is limited. Kaempferol is a natural flavonoid with various beneficial effects. In this study, our goal is to investigate the roles of kaempferol combined with umbilical cord-derived mesenchymal stem cells (UCMSCs) in IUA. UCMSCs were collected from human umbilical cords. The multilineage differentiation potential of human UCMSCs was evaluated by Oil Red O staining, Alizarin Red S staining, and Alcian Blue staining. The phenotype profile of human UCMSCs was assessed by flow cytometry. CCK-8 and Transwell assays were performed to detect cell viability and migration. The IUA rat model was established. Histological changes were examined by hematoxylin-eosin staining and Masson staining. Gene expression was evaluated by western blotting and immunofluorescence. Kaempferol (10 μM) promoted the migration and proliferation of human UCMSCs in vitro. Additionally, kaempferol/UCMSCs combination treatment recovered endometrial injury and inhibited endometrial fibrosis and epithelial-mesenchymal transition occurrence in IUA rat models. Mechanistically, kaempferol/UCMSCs combination treatment inhibited JAK2/STAT3 pathway. Kaempferol/UCMSCs combination treatment can promote the repair of damaged endometrium by decreasing endometrial fibrosis. The inactivation of JAK2/STAT3 pathway is greatly responsible for the protective effect of kaempferol/UCMSCs combination treatment.