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.

中文翻译：

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干细胞衍生的卵巢再生贴片可恢复原发性卵巢功能不全大鼠的卵巢功能并挽救其生育能力。

理由：原发性卵巢功能不全 (POI) 通常发生在 40 岁之前，并与不孕症有关。激素替代疗法通常用于治疗血管舒缩症状，但不能恢复卵巢功能或生育能力。干细胞疗法已被研究用于治疗 POI。然而，活干细胞的应用存在细胞保留/移植率低、致瘤性和免疫原性风险以及缺乏现成的可行性等缺点。方法：我们开发了一种治疗性卵巢再生贴片 (ORP)，它由临床相关的可水解支架和合成间充质干细胞 (synMSCs) 组成，它们是包裹 MSCs 分泌物组的微粒。在顺铂诱导的 POI 损伤大鼠中测试了 ORP 的治疗效力。结果：体外研究表明，ORP 刺激卵巢体细胞 (OSC) 的增殖并抑制损伤应激下的细胞凋亡。在 POI 大鼠模型中，ORP 的植入通过恢复性激素分泌、发情周期持续时间和卵泡发育来挽救生育能力。结论：ORP 代表了一种无细胞、现成的、临床上可行的 POI 治疗方法。