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Human umbilical cord mesenchymal stem cells reconstruct the vaginal wall of ovariectomized Sprague–Dawley rats: implications for pelvic floor reconstruction

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Abstract

Vaginal structural defects are involved in pelvic organ prolapse (POP). We tested whether mesenchymal stem cell (MSC) therapy can repair the weakened vaginal wall of POP patients as a novel POP treatment. Ninety-six ovariectomized rats were divided into 4 groups (n = 24/group): saline (sal), collagen (col), sal + MSC, and col + MSC groups. Two weeks after ovariectomy, rats received subepithelial injection of 0.3 ml saline, 0.3 ml collagen I gel, and 0.3 ml saline: 3 × 106 human umbilical cord mesenchymal stem cells (HUMSCs), or 0.3 ml collagen I gel: 3 × 106 HUMSCs into the anterior vaginal wall. Eight additional rats underwent in vivo bioluminescence imaging (BLI) to evaluate in vivo cell viability. The BLI signal disappeared within 1 week after MSC injection, and no in vivo MSC differentiation was found. Collagen I content was significantly lower at 4 and 12 weeks in the two MSC groups than in the sal and col groups, while collagen III was significantly higher (P < 0.001). The fraction of smooth muscle in the nonvascular muscularis increased significantly in the two MSC groups at 12 weeks (P < 0.001). ACTA2 mRNA in the col + MSC group was significantly higher than that in the sal group at 2 and 4 weeks (P = 0.042 and P = 0.040). mRNA levels of angiogenic factors (bFGF or VEGF) in the two MSC groups were significantly higher than those in the sal and col groups at different time points. HUMSCs normalized the fibromuscular structures of the vaginal wall of ovariectomized rats potentially through a paracrine effect.

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Acknowledgements

We thank the animal care staff at PUMCH for their assistance in managing the husbandry of the rats used in this study.

Funding

This study was funded by the National Natural Science Foundation of China (81801427, 81771561, 81830043) and the Beijing Municipal Natural Science Foundation (7192154).

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Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Meng Mao, Ye Zhang, Jia Kang & Lan Zhu

  2. Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Meng Mao

  3. Medical Science Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Yaqian Li

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  1. Meng Mao
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  2. Yaqian Li
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  3. Ye Zhang
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  4. Jia Kang
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  5. Lan Zhu
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Contributions

Meng Mao: Protocol development, data collection, data analysis, and manuscript writing. Yaqian Li: animal experiment and data analysis. Ye Zhang: animal experiment. Jia Kang: Data collection. Lan Zhu: Protocol development.

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Correspondence to Lan Zhu.

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Mao, M., Li, Y., Zhang, Y. et al. Human umbilical cord mesenchymal stem cells reconstruct the vaginal wall of ovariectomized Sprague–Dawley rats: implications for pelvic floor reconstruction. Cell Tissue Res 386, 571–583 (2021). https://doi.org/10.1007/s00441-021-03478-9

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