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. Similar content being viewed by others Data availability The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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The authors appreciate the help of Hubei Maternal and Child Health Hospital. Funding The work was supported by Hubei Provincial Administration of Traditional Chinese Medicine 2023–2024 Chinese Medicine Guidance Project (ZY2023F029) (Study on the mechanism of Taohong Siwu decoction in promoting mesenchymal stem cells to repair damaged endometrium and preventing intrauterine adhesion by regulating JAK/STAT3 pathway). Author information Authors and Affiliations Contributions Di Shang and Yuru Chen conceived and designed the experiments. Di Shang, Yuru Chen and Dongyan Sun carried out the experiments. Di Shang, Yuru Chen and Dongyan Sun analyzed the data. Di Shang, Yuru Chen and Dongyan Sun drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript. Di Shang and Yuru Chen conceived and designed the experiments. Di Shang, Yuru Chen and Dongyan Sun carried out the experiments. Di Shang, Yuru Chen and Dongyan Sun analyzed the data. Di Shang, Yuru Chen and Dongyan Sun drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used. Corresponding author Ethics declarations Ethical approval The experimental protocols were approved by the Ethics Committee of Hubei Maternal and Child Health Hospital (2025–029-01). Consent to participate All patients provided their written informed consent. Consent to publish Not applicable. Competing interests The authors declare that they have no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Di Shang and Yuru Chen are contributed equally to this work. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Shang, D., Chen, Y. & Sun, D. Umbilical cord-derived mesenchymal stem cells combined with kaempferol synergistically promote repair of damaged endometrium by modulating JAK2/STAT3 signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 398, 14075–14087 (2025). https://doi.org/10.1007/s00210-025-04056-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00210-025-04056-4