Journal
THERANOSTICS
Volume 11, Issue 18, Pages 8894-8908Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.61690
Keywords
primary ovarian insufficiency; ovarian regenerative patch; regenerative medicine; mesenchymal stem cells; acellular therapy; fertility
Categories
Funding
- NC State College of Veterinary Medicine
- American Heart Association
- Beijing Dongcheng Department of Science, Technology and Information [BJ-2019-103]
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The therapeutic ovarian regenerative patch (ORP) has been found to effectively treat POI and restore fertility in rats by stimulating the proliferation of ovarian somatic cells and inhibiting apoptosis under injury stress. This cell-free, off-the-shelf, and clinically feasible treatment represents a promising approach for POI.
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.
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