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Exploration of eMSCs with HA-GEL system in repairing damaged endometrium after endometrial cancer with fertility-sparing treatment

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Abstract

Despite the high complete response rate of fertility-sparing treatment in early-stage endometrial cancer (EC), the low pregnancy rate is a clinical challenge. Whether endometrium-derived mesenchymal stem cells (eMSCs) can repair damaged endometrium after EC reversal remains unclear. This study explored the potential therapeutic effects of eMSCs with suitable scaffold materials on endometrial damage caused by EC. Here, appropriate engineering scaffold materials were compared to identify the most suitable materials to carry eMSCs. Then, safety and efficacy evaluations of eMSCs with a suitable hyaluronic acid hydrogel (eMSCs/HA-GEL) were investigated in in vivo experiments with subcutaneous xenotransplantation in Balb/C nude mice and a model of endometrial mechanical injury in rats. HA-GEL has minimal cytotoxicity to eMSCs compared to other materials. Then, in vitro experiments demonstrate that eMSCs/HA-GEL enhance the inhibitory effects of progestins on EC cell biological behaviors. eMSCs/HA-GEL significantly inhibit EC cell growth and have no potential safety hazards of spontaneous tumorigenesis in Balb/C nude mouse subcutaneous xenotransplantation assays. eMSCs/HA-GEL intrauterine transplantation effectively increases endometrial thickness and glandular number, improves endometrial blood supply, reduces fibrotic areas, and improves pregnancy rates in a rat endometrial mechanical injury model. GFP-eMSCs/HA-GEL intrauterine transplantation in rats shows more GFP-eMSCs in the endometrium than GFP-eMSCs transplantation alone, and no tumor formation or suspicious cell nodules are found in the liver, kidney, or lung tissues. Our results reveal the safety and efficacy of eMSCs/HA-GEL in animal models and provide preliminary evidence for the use of eMSCs/HA-GEL as a treatment for EC-related endometrial damage.

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Data availability

All datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dr. Jiandong Ding (Department of Macromolecular Science, Fudan University, Shanghai, China) for kindly providing the 5% PLGA-PEG-PLGA.

Funding

This work was supported by the National Key Technology R&D Program of China (Grant No. 2019YFC1005200 and No. 2019YFC1005203).

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Authors and Affiliations

  1. Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, China

    Wei Liu, Mengxin Hao, Yuhui Xu, Xiaojun Ren, Jiali Hu, Lulu Wang, Xiaojun Chen & Qiaoying Lv

  2. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China

    Wei Liu, Mengxin Hao, Yuhui Xu, Xiaojun Ren, Jiali Hu, Lulu Wang, Xiaojun Chen & Qiaoying Lv

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  1. Wei Liu
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Contributions

Wei Liu: conceptualization, data curation, formal analysis, investigation, methodology, project administration, validation, writing — original draft, writing — review and editing. Mengxin Hao: conceptualization, data curation, formal analysis, investigation, methodology, project administration, validation. Yuhui Xu: resources. Xiaojun Ren: resources. Jiali Hu: resources. Lulu Wang: resources. Qiaoying Lv: data curation, formal analysis, investigation, methodology, project administration, validation, supervision, writing — review and editing. Xiaojun Chen: conceptualization, funding acquisition, investigation, project administration, supervision, writing — review and editing.

Corresponding authors

Correspondence to Xiaojun Chen or Qiaoying Lv.

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Ethics approval

This study complied with the tenets of the Declaration of Helsinki and the National Guidelines for Animal Use in Research (China) and was approved by the Ethics Committee of the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, People’s Republic of China). Animal experiments were approved by the Ethics Committees of Fudan University (approval no. 201909008S). Collection of human tissue samples was approved by the Ethics Committees of the Obstetrics and Gynecology Hospital of Fudan University (approval no. 2019–129).

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Liu, W., Hao, M., Xu, Y. et al. Exploration of eMSCs with HA-GEL system in repairing damaged endometrium after endometrial cancer with fertility-sparing treatment. Cell Tissue Res 394, 379–392 (2023). https://doi.org/10.1007/s00441-023-03831-0

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