Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress

• Human umbilical cord-derived MSCs transplantation partially restores age-related ovarian functional decline in mice by modulating the local renin-angiotensin system (RAS), specifically upregulating AT1R expression. • The ovarian local RAS is independent of systemic RAS, correlates with age and ovarian function, and is linked to inflammation and oxidative stress markers in human follicular fluid. • Co-culture with MSCs alleviates aging-induced dysfunction in KGN cells, reducing ROS and senescence while improving mitochondrial membrane potential and secretion; Ang(1–7) enhances these effects more than Ang II. • This study proposes a novel mechanism for MSC therapy in reproductive aging, highlighting the RAS pathway as a potential therapeutic target.