来自MSCs的EVs可以防止化疗引起的卵巢毒性:PI3K/AKT/mTOR轴的作用
Nehal M Elsherbiny1, Mohamed S Abdel-Maksoud2, Kousalya Prabahar3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. nelsherbiny@ut.edu.sa.
Journal of ovarian research
|November 12, 2024
概括
化疗可以导致卵巢衰竭,影响生育能力. 介酶干细胞衍生的外体细胞 (MSCs-EVs) 通过保护卵泡和恢复激素水平来保持卵巢功能,提供一种潜在的生育保护策略.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 化疗诱导的卵巢衰竭 (OF) 会导致不孕不育和雌激素缺乏.
- 目前的生育保存方法,如卵细胞冷保存,有其局限性.
- 外体,特别是那些来自介质干细胞 (MSCs-EVs) 的外体,正在探索再生应用.
研究的目的:
- 在大鼠模型中研究MSCs-EVs对化疗引起的卵巢衰竭的保护作用.
- 评估MSCs-EVs对卵巢卵泡发育,激素平衡和关键信号通路的影响.
主要方法:
- 雌性白色大鼠被诱导使用OF,并用MSCs-EVs,Rapamycin或Quercetin进行治疗.
- 卵巢功能通过组织病理学,免疫组织化学和荷尔蒙测试来评估.
- 分析了PI3K/Akt/mTOR信号通路和相关的分子标记物.
主要成果:
- 治疗MSCs-EV恢复了血清激素水平,并保留了原始毛囊和卵细胞.
- MSCs-EVs抑制了卵巢PI3K/Akt/mTOR通路,调节了特定的miRNA,并减少了亡标记物 (BAX,BCl2).
- MSCs-EVs增加了增殖标记Ki67,表明卵巢细胞活性恢复.
结论:
- 治疗MSCs-EVs是有效的预防化疗引起的卵巢衰竭.
- 在化疗期间同时治疗MSCs-EVs可以保持卵巢功能和生育能力.
- 该机制涉及抑制PI3K/Akt轴,防止毛囊过度激活,并抑制颗粒细胞细胞灭绝.
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