Role and mechanism of mesenchymal stem cells in endometrial receptivity remodeling

Endometrial receptivity (ER) is a pivotal determinant of successful embryo implantation, and its dysfunction is a major cause of infertility and recurrent implantation failure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy due to their multipotency, self-renewal capacity, and potent paracrine activity. This review elucidates the multifaceted mechanisms through which MSCs enhance ER, including direct differentiation into endometrial cells, promotion of angiogenesis via secretion of factors like VEGF, immunomodulation by inducing Treg cells and M2 macrophages, and remodeling of the extracellular matrix. Crucially, we highlight emerging clinical evidence; for instance, in a recent clinical trial, intrauterine infusion of umbilical cord-derived MSCs in women with intrauterine adhesions significantly increased endometrial thickness from a mean of 4.2 ± 0.5 mm to 6.8 ± 0.7 mm and improved the clinical pregnancy rate to 38.5%. Furthermore, we discuss ongoing clinical trials and future directions, such as the development of engineered MSC-derived exosomes and biomaterial-scaffold combinations. Despite challenges in standardization and long-term safety, MSC-based therapy represents a novel and potent approach for regenerating dysfunctional endometrium, offering new hope for refractory infertility.