由胎盘衍生的介质干细胞增加肝细胞生长因子分泌 通过Wnt信号激活通过血管重塑通过卵巢切除的老鼠模型改善卵巢功能
Hyeri Park1,2, Dae Hyun Lee1,2, Jun Hyeong You1
1Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea.
Cells
|December 9, 2023
概括
胎盘衍生的介质干细胞 (PD-MSCs) 通过增强血管改造和卵泡发育,改善了大鼠的卵巢功能. 这种治疗效果是由HGF分泌的介导,它激活了Wnt信号,并降低了血管透性.
科学领域:
- 生殖生物学和干细胞治疗.
- 血管生物学和组织再生
- 内分泌学和卵巢功能.
背景情况:
- 卵巢血管网络与卵泡发育之间的复杂关系对生殖健康至关重要.
- 连接血管改造和卵巢功能的精确治疗机制仍然不完全理解.
- 研究用于卵巢功能障碍的基于新型干细胞的策略是研究的一个重要领域.
研究的目的:
- 为了确定从胎盘衍生的介质干细胞 (PD-MSCs) 中增加的肝细胞生长因子 (HGF) 是否可以在卵巢切除的小鼠模型中改善卵巢功能.
- 阐明血管改造,特别是Wnt信号激活在PD-MSCs对卵巢功能的治疗作用中的作用.
- 评估PD-MSC移植对卵巢血管结构的影响,与Wnt信号和血管透性相关的基因表达,以及卵泡发育.
主要方法:
- 建立一个半排卵切除的老鼠模型来诱导卵巢损伤.
- 静脉内移植PD-MSCs (5 × 10^5细胞) 并随后检查卵巢组织.
- 试验室试验涉及PD-MSC与人类静脉内皮细胞 (HUVEC) 和卵巢组织的共同培养,以评估血管功能和卵泡成熟.
主要成果:
- 与对照人群相比,PD-MSC移植在受伤的卵巢组织中显著恢复了血管结构.
- 在接受PD-MSC治疗的老鼠中,Wnt信号通路基因表达 (LRP6,GSK3β,β-catenin) 被显著上调,而血管透性标记物 (Asef,ERG3) 被下调.
- 治疗PD-MSC增强了卵泡的发育和成熟,而体外研究表明,血管形成有所改善,内皮透性降低.
结论:
- 由PD-MSCs分泌的肝细胞生长因子 (HGF) 在卵巢功能障碍的小鼠模型中在改善卵巢功能方面发挥着关键作用.
- 治疗机制包括通过Wnt信号通路激活来降低血管透性,从而改善卵巢血管改造.
- PD-MSC疗法是通过向血管完整性和促进卵泡发育来增强卵巢功能的一种有前途的策略.
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