Innovations in the treatment of endometrial diseases: Role of human umbilical cord mesenchymal stem cells and their exosomes

He-Lin Wang, Shi-Dong Zhang, Ting Liu, Li-Mei Liu, Xiaoyan Pan
In: World Journal of Stem Cells · 2026 · vol. 18(5) · doi:10.4252/wjsc.v18.i5.115486 · W7162247936
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Abstract

Endometrial disorders, notably intrauterine adhesions and thin endometrium, are major causes of female infertility and are often poorly managed by conventional therapies. Human umbilical cord-derived mesenchymal stem cells and their exosomes have emerged as promising regenerative alternatives, leveraging their immunomodulatory, anti-fibrotic, and pro-angiogenic properties. This review provides a critical synthesis of evidence from 125 studies (2007-2025), focusing not only on therapeutic mechanisms and clinical progress but also on the specific hurdles that impede clinical translation. Their mechanistic actions converge on key repair processes, including immune modulation, inhibition of transforming growth factor-β/Smad-mediated fibrosis, and promotion of vascularization. Early phase clinical trials have reported improved endometrial thickness and pregnancy rates, including live births in 30.8%-38.5% of severe intrauterine adhesion cases, with initially favorable safety profiles. The efficacy is further augmented by combining it with biomaterial carriers or estrogen. However, clinical translation is significantly constrained by inherent challenges, including small-scale, heterogeneous trials with short follow-ups; manufacturing complexities due to donor variability and a critical lack of potency assays linking cell phenotype to in vivo efficacy; and unresolved safety concerns, particularly regarding long-term and intergenerational risks, ectopic tissue formation, and context-dependent pro-tumorigenic potential in conditions such as endometriosis and cancer. Therefore, future advancements hinge on addressing these interconnected fronts: Conducting mechanism-informed, large-scale clinical trials, establishing manufacturing standards integrated with biologically relevant potency assays, and resolving context-dependent efficacy and safety paradoxes.

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endometriosisinfertility

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