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中华细胞与干细胞杂志(电子版) ›› 2025, Vol. 15 ›› Issue (04) : 245 -250. doi: 10.3877/cma.j.issn.2095-1221.2025.04.008

综述

脐带间充质干细胞治疗造血干细胞移植术后卵巢早衰的研究进展
彭惊龙1,2, 张潇月2, 王红美2,()   
  1. 1261000 潍坊,山东第二医科大学临床医学院
    2250000 济南,山东第一医科大学第一附属医院 (山东省千佛山医院)儿童血液科
  • 收稿日期:2025-07-02 出版日期:2025-08-01
  • 通信作者: 王红美
  • 基金资助:
    山东省齐鲁干细胞工程有限公司研究项目(QLsco12023008)

Recent advances in umbilical cord mesenchymal stem cell therapy for premature ovarian failure following hematopoietic stem cell transplantation

Jinglong Peng1,2, Xiaoyue Zhang2, Hongmei Wang2,()   

  1. 1Department of Pediatrics, School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, China
    2Department of Pediatrics, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan 250000, China
  • Received:2025-07-02 Published:2025-08-01
  • Corresponding author: Hongmei Wang
引用本文:

彭惊龙, 张潇月, 王红美. 脐带间充质干细胞治疗造血干细胞移植术后卵巢早衰的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(04): 245-250.

Jinglong Peng, Xiaoyue Zhang, Hongmei Wang. Recent advances in umbilical cord mesenchymal stem cell therapy for premature ovarian failure following hematopoietic stem cell transplantation[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2025, 15(04): 245-250.

卵巢早衰(POF)是造血干细胞移植术后常见并发症,主要由放化疗引起的卵巢毒性损伤导致,同时涉及细胞凋亡、血管损伤、免疫微环境紊乱及氧化应激与自噬等复杂机制。POF对女性患者生育能力以及长期生活质量均有深远影响,探寻切实有效的卵巢修复方法是亟待解决的关键问题。脐带间充质干细胞(UC-MSCs)因其低免疫原性等优势,近年成为POF治疗的研究热点。临床前研究表明,UC-MSCs可通过分化与组织修复、促血管生成与抗纤维化、免疫调节与抗炎、抗氧化与调节自噬等多种机制,展现出修复卵巢功能的潜力。不同注射途径(如静脉和局部注射)均显示出显著疗效。尽管如此,目前临床研究尚处于初步阶段,仅有小规模试验和病例报道表明UC-MSCs具有一定疗效,其长期安全性和标准化治疗方案仍需进一步研究和验证。

Premature ovarian failure (POF) is a common complication after hematopoietic stem cell transplantation in patients, which is mainly caused by ovarian toxicity induced by radiotherapy and chemotherapy, and involves complex mechanisms such as cells apoptosis, vascular injury, immune microenvironmental disturbances, oxidative stress and autophagy. POF has a profound impact on female patients' fertility and long-term quality of life, searching for effective ovarian repair methods is a critical issue that needs to be urgently addressed. Umbilical cord mesenchymal stem cells (UC-MSCs) have become a hotspot for POF treatment in recent years due to their low immunogenicity and other advantages. Preclinical studies have shown that UC-MSCs demonstrate potential for repairing ovarian function through various mechanisms such as differentiation and tissue repair, promoting angiogenesis and anti-fibrosis, immune regulation and anti-inflammation, and antioxidation and autophagy regulation. Different routes of injection (e.g. intravenous and local) have shown significant efficacy. Nevertheless, clinical studies are still in the preliminary stage, only small- scale trials and case reports have demonstrated the efficacy of UC-MSCs. Their long-term safety and standardised therapeutic regimens still require further research and validation.

图1 造血干细胞移植导致卵巢早衰的相关机制(Adobe Illustrator 2023绘图软件绘制)注:ROS为活性氧;GCs为颗粒细胞;E2为雌二醇;FSH为促卵泡生成素;LH为促黄体生成素;红色箭头为直接损伤;蓝色箭头为免疫机制;绿色箭头为激素变化;虚线箭头为潜在或间接作用
表1 脐带间充质干细胞治疗POF的临床前研究总结
动物模型 造模药物 UC-MSCs类型 注射方式 研究结论 参考文献
雌性Wistar大鼠 顺铂 UC-MSCs 静脉注射 通过TGF-β1/Smad3信号通路抑制卵巢组织纤维化有助于卵巢功能的恢复。 Cui等[21]
雌性Wistar大鼠 顺铂 UC-MSCs 静脉注射 通过调节AMPK/mTOR自噬通路降低TICs自噬水平,减轻TICs的凋亡 Lu等[22]
雌性Wistar大鼠 顺铂 缺氧预处理的UC-MSCs 静脉注射 可诱导外泌体的总蛋白浓度显著增加,通过靶向PTEN/PI3K/AKT/mTOR信号通路,通过miR-205-5p的转移,增强血管生成 Qu等[30]
雌性C57BL/6小鼠 环磷酰胺/白消安 HO-1/shho-1-UC-MSCs 静脉注射 可激活JNK/Bc1-2信号通路调控的自噬,上调CD8+ CD28- T细胞循环 Yin等[23]
雌性C57BL/6J小鼠 环磷酰胺 HUC-MSCs 静脉注射 调节GSK-3β介导的卵泡细胞线粒体动态平衡,减少GSK-3β表达,减轻卵巢损伤 Xiong等[31]
雌性西藏微型猪 环磷酰胺 UC-MSCs 静脉注射 降低卵巢细胞凋亡率,增加p-AKT、p-ERK1/2和BAX的表达,降低Bcl-2的表达,改善卵巢早衰 Cai等[32]
雌性C57BL/6小鼠 环磷酰胺 胶原支架/UC-MSCs 卵巢局部注射 促进颗粒细胞的增殖,促进卵巢血管生成,增加CD31表达 Yang等[19]
雌性C57BL/6J小鼠 乙烯基环己烯二氧化物 UC-MSCs/HA 卵巢局部注射 延长UC-MSCs在卵巢中的滞留时间,增强其分泌功能,激活PI3K-AKT通路,促进卵泡存活 Jiao等[28]
雌性SD大鼠 环磷酰胺 3D UC-MSCs球体 卵巢局部注射 刺激血管内皮生长因子及其他营养因子(HGF、EGF等)分泌,更能通过旁分泌作用改善POF,降低氧化应激,阻止GCs的凋亡和自噬的能力 Dai等[29]
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