Feasibility and mechanism study of human umbilical cord mesenchymal stem cells for the treatment of premature ovarian insufficiency

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian insufficiency that occurs before the age of 40 years in women and is characterized by menstrual abnormalities (amenorrhea, scanty menstruation), follicle stimulating hormone (FSH) > 25 U/L, fluctuating estrogen levels, and a common endocrine disease leading to infertility. POI is associated with genetic, infectious, environmental, medical, and immunological factors. Currently, hormone replacement therapy is the main clinical intervention for POI, but it cannot fundamentally restore ovarian follicular reserve and fertility potential. Human umbilical cord mesenchymal stem cells (hUCMSCs) have attracted extensive attention in the field of regenerative medicine due to their advantages of easy access, low immunogenicity, and multi-directional differentiation potential. Accumulating preclinical studies have confirmed that hUCMSCs could significantly improve ovarian function, endocrine profiles, and quality of life, but there is a lack of systematic collation and summary of its core regulatory mechanisms and research progress, which restricts the translation of related technologies into clinical practice. The literature retrieval was conducted in the PubMed, Embase, Web of Science, and CNKI databases for articles published within the past 10 years (from 2016 to 2025) using the key search terms: “human umbilical cord mesenchymal stem cells”, “premature ovarian insufficiency”, “Transplantation”, “ Stem Cell Homing” and “ Ovarian granulosa cells”. The inclusion criteria covered original research articles, randomized controlled trials, and, randomized controlled trials, and meta-analyses focusing on the mechanism exploration and clinical application of human umbilical cord mesenchymal stem cells in premature ovarian insufficiency. The exclusion criteria included duplicate publications, review articles with no original data, and studies with unclear intervention protocols. Relevant preclinical and clinical trials are being conducted in an orderly manner, but based on the complexity of the therapeutic mechanisms of hUCMSCs, they have not been fully elucidated. We clarify that existing basic research has confirmed the reparative potential of hUCMSCs for POI. However, most relevant studies are limited to animal experiments, with a lack of large-sample, multicenter clinical trials. Key issues including standardized administration protocols and long-term safety evaluation still need further exploration.