In women of reproductive age, severe injuries to the ovary are often accompanied by premature ovarian failure (POF), which can result in amenorrhea or infertility. Hormone replacement therapy has been used to treat POF; however, it has limited therapeutic efficiency and may cause several side effects. In this study, we aimed to fabricate a Matrigel scaffold loaded with human umbilical cord-derived mesenchymal stem cells (MSCs) and explore its potential to restore ovarian function and repair ovarian structures in vitro and in vivo. POF mouse models were established by injecting mice with cyclophosphamide for 15 consecutive days. Then, MSC/Matrigel was transplanted into the ovaries of the mice. Five weeks later, the morphology of the ovaries and follicles was observed by hematoxylin/eosin staining, and the tissue fibrosis ratio was measured using Masson's trichrome staining. The number of blood vessels was evaluated by α-smooth muscle actin and CD31 immunofluorescence, and Ki67 expression was used to determine the proliferation of granulosa cells. The expression of vascular endothelial growth factor (VEGF)-A was assessed by western blotting. The Matrigel scaffold regulated the expression of VEGF-A in vitro. Moreover, it promoted MSC survival and proliferation and prevented MSC apoptosis in vivo. After the transplantation of the MSC/Matrigel, the number of follicles was significantly increased in the mice with POF, and the tissue fibrosis ratio was reduced. Furthermore, the MSC/Matrigel significantly improved the proliferation rate of granulosa cells, increased the number of blood vessels, and upregulated the expression of VEGF-A. These findings demonstrate that MSC/Matrigel may support follicular development and help restore ovarian structures in vivo.

中文翻译：

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在卵巢早衰小鼠模型中，基质胶/脐带来源的间充质干细胞促进颗粒细胞增殖和卵巢血管化

在育龄妇女中，卵巢的严重损伤通常伴有卵巢早衰（POF），这可能导致闭经或不孕。激素替代疗法已用于治疗 POF；然而，它的治疗效率有限，可能会引起一些副作用。在本研究中，我们旨在制造一种载有人脐带间充质干细胞 (MSCs) 的基质胶支架，并探索其在体外和体内恢复卵巢功能和修复卵巢结构的潜力。通过连续15天给小鼠注射环磷酰胺建立POF小鼠模型。然后，将 MSC/Matrigel 移植到小鼠的卵巢中。五周后，苏木精/伊红染色观察卵巢和卵泡的形态，组织纤维化率采用Masson三色染色法测定。用α-平滑肌肌动蛋白和CD31免疫荧光检测血管数量，用Ki67表达判断颗粒细胞增殖情况。通过蛋白质印迹评估血管内皮生长因子（VEGF）-A的表达。Matrigel 支架在体外调节 VEGF-A 的表达。此外，它在体内促进 MSC 存活和增殖并防止 MSC 凋亡。移植MSC/Matrigel后，POF小鼠的卵泡数量明显增加，组织纤维化率降低。此外，MSC/Matrigel 显着提高了颗粒细胞的增殖率，增加了血管数量，并上调了 VEGF-A 的表达。