Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys
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.
Authors
- Man Teng (ORCID: https://orcid.org/0000-0003-2784-4169)
- Yan Zhao (ORCID: https://orcid.org/0000-0002-4588-6752)
- Linli Hu (ORCID: https://orcid.org/0000-0001-9069-2466)
- Xueyu Chen (ORCID: https://orcid.org/0000-0002-7066-0501)
- Jiaqi Wu (ORCID: https://orcid.org/0000-0001-7737-5597)
- Qiong Ke (ORCID: https://orcid.org/0000-0003-2566-7242)
- Jinglei Zhai (ORCID: https://orcid.org/0000-0002-9459-8781)
- Zhenyu Xiao (ORCID: https://orcid.org/0000-0003-4445-8219)
- Hongmei Wang (ORCID: https://orcid.org/0000-0002-5881-2488)
- Wan Tu
- Xuehan Zhao (ORCID: https://orcid.org/0009-0006-4129-1571)
- Xiaokui Yang (ORCID: https://orcid.org/0000-0001-8592-9262)
- Yan Long (ORCID: https://orcid.org/0000-0001-9274-7950)
- Jun Wu (ORCID: https://orcid.org/0000-0002-6346-4756)
- Hao Wu (ORCID: https://orcid.org/0000-0002-8396-7393)
- Haifeng Wan (ORCID: https://orcid.org/0000-0002-1409-9027)
- Yingying Qin (ORCID: https://orcid.org/0000-0002-0319-7799)
- Fan Guo (ORCID: https://orcid.org/0000-0002-0165-073X)
- Qiqian Wu
- Hua Yang (ORCID: https://orcid.org/0000-0002-0153-582X)
- Yingpu Sun (ORCID: https://orcid.org/0000-0002-1622-1612)
- Wenzhe Zhang (ORCID: https://orcid.org/0000-0001-7596-3715)
- Beijia He
- Shanjun Dai
- Lan Zhu
- Wei Luo (ORCID: https://orcid.org/0000-0001-7136-0140)
Institutions
- Beijing Institute of Technology (CN)
- Shandong University (CN)
- Sun Yat-sen University (CN)
- Capital Medical University (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Shenzhen Maternity and Child Healthcare Hospital (CN)
- Shandong Provincial Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Shandong First Medical University (CN)
- Beijing Obstetrics and Gynecology Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
- State Key Laboratory of Stem Cell and Reproductive Biology
- Southern Medical University (CN)
Publication Details
- Journal
- Cell Discovery
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1038/s41421-024-00726-4
- Citations
- 14
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 7.60
Funders
- Chinese Academy of Sciences
- Natural Science Foundation of Beijing Municipality