Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice

• Identified a novel LRP1high subpopulation within human UC-MSCs that significantly improves ovarian function in both aged and chemotherapy-induced POF mouse models. • The LRP1high subpopulation exerts therapeutic effects via unique secretory functions, including chemokines, cytokines, and growth factors, and by remodeling the extracellular matrix. • Single-cell RNA sequencing revealed three distinct functional subtypes in UC-MSCs, highlighting the importance of subpopulation selection for effective stem cell therapy. • Mechanistically, the LRP1high subpopulation modulates oocyte extracellular matrix, NAD metabolism, and mitochondrial function in granulosa cells, offering new targets for POF treatment.