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Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation

作者:Zhengli Zhou, Xiaomei Wu, Tingwei Chen, Bo Zhang, Wenxin Li, Min Zhou, Jingxue Zhao, Erdan Dong, Tianqing Li · 发表于:Stem Cell Research & Therapy · 年份:2024 · DOI:10.1186/s13287-024-03788-z · 被引用次数:12 · 研究领域:Gynecological conditions and treatments、Reproductive System and Pregnancy、Endometriosis Research and Treatment

BACKGROUND: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA. METHODS: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis. RESULTS: We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of me...