Advantages of Allogeneic Mesenchymal Stem Cells as an Innovative Therapy in Patients with Endometrium Dysfunction

Is it reasonable to use allogeneic mesenchymal stem cells (MSCs) therapy for thin endometrium and recurrent implantation failure? Thin endometrium (TE) and recurrent implantation failure (RIF) are associated with poor reproductive outcomes. Single-cell RNA sequencing (scRNA-seq) shows that such pathologies involve functional impairment of endometrial stromal, vascular, immune cells rather than reductions in cell numbers. MSCs exert regenerative and immunomodulatory effects and are proposed as candidates for endometrial repair. scRNA-seq studies indicate that TE and RIF are characterized by stromal progenitor dysfunction, impaired angiogenesis, immune dysregulation, and cellular senescence, providing a biological rationale for investigating allogeneic MSC-based therapies. scRNA-seq studies of human endometrium in patients with TE and RIF are reviewed alongside experimental and clinical studies evaluating autologous and allogeneic MSCs, with particular emphasis on umbilical cord-derived MSCs. Transcriptomic analyses consistently demonstrate reduced proliferation and decidualization of endometrial stromal cells, suppression of angiogenesis, immune dysregulation, and activation of senescence-associated genes. Preclinical studies show that MSC administration restores endometrial structure, vascularization, and receptivity markers. Early clinical studies suggest potential benefit, although data remain limited and heterogeneous due to non-randomized studies. Allogeneic MSCs are promising as therapy, but further studies on mechanisms and clinical validation are needed.