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Evaluation of Safety and Efficacy of Amniotic Mesenchymal Stem Cells for POI in Animals

  • Regenerative Medicine: Original Article
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Abstract

The efficacy of human amniotic mesenchymal stem cell (hAMSC) ovarian injection in improving ovarian function in primary ovarian insufficiency (POI) patients has been shown in some reports. However, the safety and efficacy of hAMSC vein injection remains unclear. In this study, we evaluated the safety and efficacy of hAMSC intravenous injection in cynomolgus macaques and SD rats and provided evidence for clinical trials. The hAMSCs were transplanted three times in SD rats at low, medium, and high doses. The animal behavior and biochemical and biophysical parameters were routinely monitored on a 2-month period posttransplantation, and histopathologic examinations were also performed. Experiments on the acute toxicity, allergy test, and hemolysis test showed that hAMSCs possess good biocompatibility. Our results showed that the maximum tolerated dose of hAMSCs in SD rats was 4.0 × 107 cells/kg. The maximum safe dose with three injections of hAMSCs in SD rats was 5.0 × 106 cells/kg. In addition, the results demonstrated that hAMSCs may restore POI rat ovarian function after two injections of 2.5 × 106 cells/kg or 5.0 × 106 cells/kg, which improved the disturbed estrous cycle, hormone levels, and ovarian lesions induced by pZP3. In conclusion, the preclinical results suggested that the transplantation of hAMSCs may be safe and efficacious for SD rats at doses of 5.0 × 106 cells/kg and lower.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

We thank the donors of stem cells, the Department of Obstetrics and Gynaecology in The Second Hospital of University of South China and Tianjin Tiancheng New Drug Evaluation.

Funding

This work was supported by Scientific and Technological Innovation Program of High-tech Industry of Hunan Province (NO: 2020GK4082), Changsha Key Research And Development Program (NO: kh2201247), Loudi Key Generic technologies Program (NO: Lou Caijiao No. 1 [2022]).

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Author notes

  1. Yuan Yang and Li Li contributed equally to this work.

Authors and Affiliations

  1. Hunan Yuanpin Cell Technology Co. Ltd. (Yuanpin Biotech), Changsha, 410100, Hunan, China

    Yuan Yang, Tenglong Yan, Jiangzhou Hua, Shiping Li, Yun Liu, Sijie Yu, Zhigang Xue & Chunbing Zheng

  2. Changsha Institute of Industrial Technology for Stem Cell and Regenerative Medicine, Changsha, 410100, China

    Yuan Yang, Tenglong Yan, Jiangzhou Hua, Shiping Li, Yun Liu, Sijie Yu, Zhigang Xue & Chunbing Zheng

  3. Changsha Health Vocational College, Changsha, 410100, Hunan, China

    Li Li

  4. Loudi Central Hospital, Loudi, 417000, Hunan, China

    Hongmei Zhang, Shihuan Tang & Xianping Zhang

  5. Department of Regenerative Medicine, Translational Center for Stem Cell Research, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China

    Zhigang Xue

Authors
  1. Yuan Yang
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  2. Li Li
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Contributions

Yuan Yang analyzed most of the data and wrote the initial draft of the paper; Li Li, Tenglong Yan, Jiangzhou Hua, Shiping Li, Yun Liu, and Sijie Yu analyzed the data and interpreted the results; Hongmei Zhang and Shihuan Tang acquired resources; Zhigang Xue, Xianping Zhang, and Chunbing Zheng conceived the idea of the study; all authors discussed the results and revised the manuscript.

Corresponding authors

Correspondence to Xianping Zhang or Chunbing Zheng.

Ethics declarations

Ethics Approval and Consent to Participate

The Animal Ethic Committee of Tianjin Tiancheng New Drug Evaluation approved the acute toxicity assay (NO: 2021120102), long toxicity and tissue distribution assay (NO: 2022022802), allergy test (NO: 2022051801), cynomolgus macaque assay (NO: 2021120102), POI rats assay (NO: 2022030703), and the Ethic Committee of the Second Hospital of University of South China approved the collection of amniotic membrane sample (NO: 202208–01).

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Written informed consent for publication was obtained from all participants.

Competing Interests

The authors declare no competing interests.

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Highlights

1. hAMSC may restore POI rat ovarian function.

2. hAMSC did not cause haemolysis.

3. Multiple transplantation of hAMSC may be safe for SD rats at doses of 5.0 × 106 cells/kg and lower.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 638 KB)

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Yang, Y., Li, L., Yan, T. et al. Evaluation of Safety and Efficacy of Amniotic Mesenchymal Stem Cells for POI in Animals. Reprod. Sci. 31, 1159–1169 (2024). https://doi.org/10.1007/s43032-023-01417-3

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  • DOI: https://doi.org/10.1007/s43032-023-01417-3

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