Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea.
PLABiologics Co., Ltd., Seongnam-si 13522, Gyeonggi-do, Republic of Korea.
Cells. 2023 Nov 25;12(23):2708. doi: 10.3390/cells12232708.
The vascular network contributes to the development of follicles. However, the therapeutic mechanism between vascular remodeling and ovarian functions is still unclear. Therefore, we demonstrated whether increased by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in an ovariectomized rat model via vascular remodeling by signaling activation. We established a half-ovariectomized rat model in which damaged ovaries were induced by ovariectomy of half of each ovary, and PD-MSCs (5 × 10 cells) were transplanted by intravenous injection. Three weeks after transplantation, rats in all groups were sacrificed. We examined the secretion of by PD-MSCs through culture medium. The vascular structure in injured ovarian tissues was restored to a greater extent in the PD-MSC transplantation (Tx) group than in the nontransplantation (NTx) group (* < 0.05). The expression of genes related to signaling (e.g., , , ) was significantly increased in the Tx group compared to the NTx group (* < 0.05). However, the expression of genes related to vascular permeability (e.g., , ) was significantly decreased in the Tx group compared to the NTx group (* < 0.05). Follicular development was improved in the Tx group compared to the NTx group (* < 0.05). Furthermore, to evaluate vascular function, we cocultivated PD-MSCs after human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and we analyzed the vascular formation assay and dextran assay in HUVECs. Cocultivation of PD-MSCs with injured HUVECs enhanced vascular formation and decreased endothelial cell permeability (* < 0.05). Also, cocultivation of PD-MSCs with explanted ovarian tissues improved follicular maturation compared to cocultivation of the Wnt inhibitor-treated PD-MSCs with explanted ovarian tissues. Therefore, secreted by PD-MSCs improved ovarian function in rats with ovarian dysfunction by decreasing vascular permeability via Wnt signaling.
血管网络有助于卵泡的发育。然而，血管重塑与卵巢功能之间的治疗机制尚不清楚。因此，我们通过 Wnt 信号激活来证明胎盘来源的间充质干细胞（PD-MSCs）增加 是否可以改善卵巢切除大鼠模型中的卵巢功能。我们建立了半卵巢切除大鼠模型，通过半卵巢切除术诱导一半卵巢受损，然后通过静脉注射移植 PD-MSCs（5×10 个细胞）。移植后 3 周，处死所有组别的大鼠。我们通过培养物检查 PD-MSCs 分泌的 。与非移植（NTx）组相比，PD-MSC 移植（Tx）组受损卵巢组织中的血管结构得到了更大程度的恢复（* < 0.05）。与 NTx 组相比，Tx 组中与 Wnt 信号相关的基因（例如 、 、 ）的表达显著增加（* < 0.05）。然而，与 NTx 组相比，Tx 组中与血管通透性相关的基因（例如 、 ）的表达显著降低（* < 0.05）。与 NTx 组相比，Tx 组中的卵泡发育得到改善（* < 0.05）。此外，为了评估血管功能，我们在脂多糖（LPS）后将 PD-MSCs 与人脐静脉内皮细胞（HUVECs）共培养，并分析 HUVECs 的血管形成测定和葡聚糖测定。与受损的 HUVECs 共培养的 PD-MSCs 增强了血管形成并降低了内皮细胞通透性（* < 0.05）。此外，与 Wnt 抑制剂处理的 PD-MSCs 共培养的卵巢组织相比，与 PD-MSCs 共培养的卵巢组织中卵泡成熟得到改善。因此，PD-MSCs 分泌的 通过 Wnt 信号降低血管通透性来改善卵巢功能障碍大鼠的卵巢功能。
