Zhang JN, Tian S, Guo XM, Zhang Q, Shang J, Yao YQ. Therapeutic potential of umbilical cord-derived mesenchymal stem cells in ameliorating ovarian aging: Insights from single-cell analysis. World J Stem Cells 2026; 18(10): 119325 [DOI: 10.4252/wjsc.119325]
Corresponding Author of This Article
Yuan-Qing Yao, Senior Department of Obstetrics and Gynecology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100010, China. yao_yuanqing@126.com
Research Domain of This Article
Obstetrics & Gynecology
Article-Type of This Article
research-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Oct 26, 2026; 18(10): 119325 Published online Oct 26, 2026. doi: 10.4252/wjsc.119325
Therapeutic potential of umbilical cord-derived mesenchymal stem cells in ameliorating ovarian aging: Insights from single-cell analysis
Jin-Ning Zhang, Shuang Tian, Xin-Meng Guo, Qi Zhang, Jin Shang, Yuan-Qing Yao
Jin-Ning Zhang, Shuang Tian, Qi Zhang, Yuan-Qing Yao, Senior Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing 100010, China
Jin-Ning Zhang, Medical School of Chinese PLA, Beijing 100039, China
Xin-Meng Guo, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Jin Shang, Reproductive Medical Center, The Ninth Medical Center of PLA General Hospital, Beijing 100101, China
Co-first authors: Jin-Ning Zhang and Shuang Tian.
Author contributions: Zhang JN and Tian S contributed equally to this manuscript and are co-first authors. Zhang JN and Tian S designed the research study, conducted experiments, and analyzed the data; Guo XM, Zhang Q, Shang J, and Yao YQ performed the research; and all authors contributed to editorial changes in the manuscript, and read and approved the final manuscript.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Institutional animal care and use committee statement: This study was approved by the Institutional Animal Care and Use Committee of Chinese PLA General Hospital, approval No. SQ2020056.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Corresponding author: Yuan-Qing Yao, Senior Department of Obstetrics and Gynecology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100010, China. yao_yuanqing@126.com
Received: April 22, 2026 Revised: June 16, 2026 Accepted: October 20, 2026 Published online: October 26, 2026 Processing time: 186 Days and 21.9 Hours
Abstract
BACKGROUND
Ovarian aging, characterized by follicle depletion and declining oocyte quality, significantly contributes to infertility in women of advanced maternal age. Mesenchymal stem cells (MSCs) offer a promising therapeutic strategy, although their precise mechanisms of action remain poorly understood.
AIM
To investigate the therapeutic effects of umbilical cord-derived MSCs (UCMSCs) on ovarian aging and to elucidate the underlying cellular and molecular mechanisms through single-cell transcriptomic analysis.
METHODS
Aged female ICR mice (10-11 months) were allocated into aged control and UCMSC transplantation (A-MSC) groups, along with young controls for comparison. A-MSC mice received tail vein injections of UCMSCs. Ovarian function was evaluated through estrous cycle monitoring, follicle counting, hormone assays, and assessment of oocyte quality (mitochondrial function, spindle morphology, aneuploidy). Single-cell RNA sequencing (scRNA-seq) was conducted on ovarian tissues to analyze transcriptional changes, cell-cell communication, and granulosa cell (GC) trajectories.
RESULTS
Transplantation of UCMSCs resulted in improved estrous cycle regularity, increased total and antral follicle counts, normalized levels of follicle-stimulating hormone, anti-Müllerian hormone, and estradiol, and enhanced yield of metaphase II oocytes. Oocyte quality improved, evidenced by higher mitochondrial membrane potential, increased mitochondrial DNA copy number, and reduced reactive oxygen species levels. scRNA-seq analysis indicated that UCMSCs primarily targeted granulosa and stromal cells, upregulating oxidative phosphorylation pathways and downregulating aging-related pathways (e.g., p53, mechanistic target of rapamycin complex 1, Wnt). Notably, the anti-aging gene Klotho was significantly upregulated. Cell communication analysis revealed a reduction in inflammatory signaling (e.g., transforming growth factor-β), and pseudotime analysis suggested that UCMSCs redirected GC fate away from a pro-inflammatory state.
CONCLUSION
UCMSCs mitigate ovarian aging by enhancing mitochondrial function, upregulating Klotho, remodeling intercellular communication, and influencing GC fate. These findings offer mechanistic insights into MSC-based therapies for age-related ovarian decline.
Core Tip: This study demonstrates that umbilical cord-derived mesenchymal stem cells (UCMSCs) effectively alleviate ovarian aging in aged mice and enhance oocyte quality. Single-cell transcriptomic analysis revealed that UCMSC treatment led to increased mitochondrial oxidative phosphorylation, elevated Klotho expression, and suppression of aging-related pathways. Additionally, UCMSCs improved intercellular communication within the ovary and influenced the developmental trajectory of granulosa cells. These findings elucidate the mechanisms underlying UCMSC-mediated ovarian rejuvenation and highlight their therapeutic potential for addressing age-related ovarian decline.
