Theranostics 2021; 11(18):8894-8908. doi:10.7150/thno.61690 This issue

Research Paper

A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency

Sichen Zhang1,2,3,4, Dashuai Zhu2,3, Zhenhua Li2,3, Ke Huang2,3, Shiqi Hu2,3, Halle Lutz2,3, Mengjie Xie1,2,3,4, Xuan Mei2,3, Junlang Li2,3, Genevieve Neal-Perry5, Shaowei Wang1,4✉, Ke Cheng2,3,6✉

1. Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China. NO.1 DaHua Road, Dong Dan, Beijing 100730, P. R. China.
2. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA.
3. Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
4. Peking Union Medical College, Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College. No. 9 Dong Dan Santiao, Beijing 100730, P.R. China.
5. Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
6. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Zhang S, Zhu D, Li Z, Huang K, Hu S, Lutz H, Xie M, Mei X, Li J, Neal-Perry G, Wang S, Cheng K. A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency. Theranostics 2021; 11(18):8894-8908. doi:10.7150/thno.61690. Available from https://www.thno.org/v11p8894.htm

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Abstract

Graphic abstract

Rationale: Primary ovarian insufficiency (POI) normally occurs before age 40 and is associated with infertility. Hormone replacement therapy is often prescribed to treat vasomotor symptom, but it cannot restore ovarian function or fertility. Stem cell therapy has been studied for the treatment of POI. However, the application of live stem cells has suffered from drawbacks, such as low cell retention/engraftment rate, risks for tumorigenicity and immunogenicity, and lack of off-the-shelf feasibility.

Methods: We developed a therapeutic ovarian regenerative patch (ORP) that composed of clinically relevant hydrolysable scaffolds and synthetic mesenchymal stem cells (synMSCs), which are microparticles encapsulating the secretome from MSCs. The therapeutic potency of ORP was tested in rats with cisplatin induced POI injury.

Results: In vitro studies revealed that ORP stimulated proliferation of ovarian somatic cells (OSCs) and inhibited apoptosis under injury stress. In a rat model of POI, implantation of ORP rescued fertility by restoring sexual hormone secretion, estrus cycle duration, and follicle development.

Conclusion: ORP represents a cell-free, off-the-shelf, and clinically feasible treatment for POI.

Keywords: primary ovarian insufficiency, ovarian regenerative patch, regenerative medicine, mesenchymal stem cells, acellular therapy, fertility