LRP1high subpopulation of human umbilical cord mesenchymal stem cell (hUC-MSC)transplantationimproves ovarian function in POF and aging mice
This study revealed the heterogeneity of UC-MSCs using single-cell sequencing technology (10x Genomics). Through in vitro and in vivo experiments, it was determined that the LRP1high UC-MSCs subpopulation has therapeutic effects in improving ovarian function. This finding provides theoretical support for the screening of stem cell preparations for use in POF, aiming to reduce the impact of other interfering cell components on ovarian tissue and provide precise, safe, and effective clinical strategies for stem cell therapy in POF. Mechanistic exploration further revealed that the LRP1high UC-MSCs subpopulation primarily improves mitochondrial function of granulosa cells by modulating DNA damage pathways, extracellular matrix-related signals, and cellular metabolism. Consequently, it more effectively enhances the quality of aging mouse oocytes, offering new insights into targeting LRP1high UC-MSCs for precise treatment of premature ovarian failure. Overall design: Female young mice (6-8 weeks), elderly mice (18 months), and elderly mice with different subgroups of UC-MSCs (unsorted, LRP1high, and LRP1low) were transplanted for 3 weeks. Cervical dislocation was euthanized, and the ovaries were decomposed to collect MII oocytes and granulosa cells for RNA sequencing.