Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys.

IF 13 1区 生物学 Q1 CELL BIOLOGY Cell Discovery Pub Date : 2024-11-05 DOI:10.1038/s41421-024-00726-4
Long Yan, Wan Tu, Xuehan Zhao, Haifeng Wan, Jiaqi Wu, Yan Zhao, Jun Wu, Yingpu Sun, Lan Zhu, Yingying Qin, Linli Hu, Hua Yang, Qiong Ke, Wenzhe Zhang, Wei Luo, Zhenyu Xiao, Xueyu Chen, Qiqian Wu, Beijia He, Man Teng, Shanjun Dai, Jinglei Zhai, Hao Wu, Xiaokui Yang, Fan Guo, Hongmei Wang
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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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干细胞移植延长了自然衰老猴的生殖寿命。
卵巢对女性的生殖和健康至关重要,因为它能产生卵母细胞并分泌性激素。移植间充质干细胞(MSCs)已被证明能缓解卵巢的病理性衰老。然而,间充质干细胞是否对自然衰老的卵巢有益尚不清楚。在这项研究中,我们首先考察了中国女性围绝经期卵巢储备的动态变化。利用自然衰老的猕猴(Macaca fascicularis)模型,我们发现将来源于人类胚胎干细胞的间充质干细胞样细胞(我们称之为M细胞)移植到衰老的卵巢中,能显著减少卵巢纤维化和DNA损伤,增强性激素分泌,提高生育能力。令人鼓舞的是,M细胞移植后,一只健康的小猴子诞生了。此外,单细胞 RNA 测序分析和体外功能验证表明,M 细胞移植后,颗粒细胞和基质细胞的凋亡、氧化损伤、炎症和纤维化得到缓解。总之,这些发现证明了M细胞移植对衰老卵巢的有益影响,并拓展了我们对卵巢衰老和干细胞缓解这一过程的分子机制的理解。
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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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