Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging

• Published in: Stem cell research & therapy 2024-03, Vol.15 (1), p.58-58, Article 58
• Main Authors: Shin, Eun-Young, Jeong, Suji, Lee, Jeoung Eun, Jeong, Dong Seok, Han, Dong Keun, Hong, Seok-Ho, Lee, Dong Ryul
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Aging; Apoptosis; Bone marrow; Cell growth; Cell therapy; Comparative analysis; Cytokines; Embryo cells; Embryogenesis; Embryonic stem cells; Estradiol; Ethylenediaminetetraacetic acid; Experiments; Fecundity; Females; Fertility; Fertility preservation of natural aging female; Fibrosis; Follicles; Human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs); Laboratory animals; Menopause; Myeloid-derived suppressor cells (MDSCs); Ovarian function; Ovaries; Progenitor cells; Reproductive senescence; Reproductive status; Senescence; Stem cells; Suppressor cells; Transplantation
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-024-03684-6

Currently, no approved stem cell-based therapies for preserving ovarian function during aging. To solve this problem, we developed a long-term treatment for human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs). We investigated whether the cells retained their ability to resist ovarian aging, which leads to delayed reproductive senescence. In a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs benefit the long-term maintenance of reproductive fecundity and ovarian reservoirs and how their transplantation regulates ovarian function. The number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice who underwent multiple introductions of hESC-MPCs compared to age-matched controls. The estradiol levels in the hESC-MPCs group were restored to those in the young and adult groups. Embryonic development and live birth rates were higher in the hESC-MPC group than in the control group, suggesting that hESC-MPCs delayed ovarian senescence. In addition to their direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via the suppression of myeloid-derived suppressor cells (MDSCs) produced in the bone marrow. Multiple introductions of hESC-MPCs could be a useful approach to prevent female reproductive senescence and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.