Revolutionizing Stem Cell Therapy: A Comparative Analysis of Diverse Mesenchymal Stem Cells for Enhanced Endometrial Regeneration

Background: Endometrial injury, particularly intrauterine adhesions (Asherman’s syndrome), represents a prevalent condition that significantly compromises female fertility. Current clinical interventions predominantly involve hysteroscopic surgery, followed by the placement of intrauterine barriers and the administration of oral estrogen to facilitate endometrial regeneration. Nevertheless, in patients with severe intrauterine adhesions, postoperative pregnancy rates remain low, ranging from 22.2% to 33.3%. Mesenchymal stem cells (MSCs), owing to their multilineage differentiation potential and tissue repair capabilities, have emerged as promising candidates for the treatment of regenerative disorders. This study aimed to compare the efficacy of MSCs derived from bone marrow, umbilical cord, adipose tissue, and decidua in the repair of damaged endometrium. Methods: The proliferation capabilities of decidual MSCs, umbilical cord MSCs, bone marrow MSCs, and adipose-derived MSCs at passages 1, 3, and 5 were evaluated using a CCK8 assay. In vitro, cytokine-induced differentiation was employed to stimulate MSCs, and the expression of epithelial cell surface markers was assessed through immunofluorescence and Western blot analyses to compare their potential for differentiation into endometrial epithelial cells. In vivo, an intrauterine adhesion rat model received MSC infusions, and the restoration of endometrial morphology was subsequently examined and compared across the different treatment groups. Results: Bone marrow MSCs demonstrated the highest proliferation rate, while adipose-derived MSCs exhibited the lowest. Notably, decidual MSCs displayed a significantly enhanced capacity to differentiate into endometrial epithelial cells compared to MSCs from other sources. Furthermore, in a rat model of intrauterine adhesion, treatment with decidual MSCs resulted in the most pronounced improvement in endometrial repair. Conclusions: Decidual MSCs demonstrate superior in vitro differentiation into endometrial epithelial cells and exhibit the most effective in vivo repair of damaged endometrial tissue, potentially mediated by the secretion of various cytokines and immunomodulatory mechanisms. This study provides critical theoretical and experimental evidence supporting the clinical application of decidual MSCs in endometrial repair. Despite certain limitations, such as the absence of clinical validation, decidual MSCs present a promising novel therapeutic strategy for intrauterine adhesions and other conditions related to endometrial injury. Future clinical trials and mechanistic studies are necessary to further validate their therapeutic potential.