Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys.
Abstract
The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.
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Research summary
The paper addresses the effects of mesenchymal stem cell transplantation on ovarian aging, which is directly related to reproductive longevity and the aging process in females. It explores potential interventions that could mitigate age-related decline in ovarian function, thus contributing to the understanding of aging mechanisms. However, while the findings are promising, they represent a solid but limited advance in the field, primarily focused on a specific model and intervention without broader implications for general longevity research.
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