Mol Ther Nucleic Acids：人羊膜上皮细胞外泌体有效促进卵巢功能恢复

生物_医药_科研 2019-07-10

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卵巢早衰（POF）是指40岁前卵巢功能停止，伴有闭经、血促性腺激素水平升高和雌激素水平降低和不孕症，也是接受化疗的女性肿瘤患者最常见的并发症之一，需要采取先进的治疗策略。最新研究报道了人羊膜上皮细胞（hAEC）衍生的外泌体可以通过转移microRNA(miRNA)抵抗细胞凋亡，从而实现卵巢功能的恢复。相关研究结果发表在Molecular Therapy-Nucleic Acids杂志上。

人羊膜上皮细胞在治疗多种疾病中显示出介导组织再生的能力，越来越多的证据表明hAEC的治疗效果主要取决于旁分泌作用。该研究鉴定了源自hAEC的外泌体，并研究了hAEC源外泌体对化疗诱导的POF小鼠中卵泡发育和卵巢功能的影响。研究结果显示，hAEC外泌体可显著增加POF小鼠的卵泡数量和改善卵巢功能。在移植早期，hAEC外泌体显著抑制颗粒细胞凋亡，保护卵巢脉管系统免受损伤，并参与维持受损卵巢中原始卵泡的数量。进一步发现富集的miRNA存在于hAEC外泌体中，因此，hAEC衍生的外泌体具有通过转移miRNA实现恢复化疗诱导的POF小鼠卵巢功能的潜力。

该项研究表明，hAECs改善卵巢功能可能源于外泌体的作用，提示未来或可利用hAEC源外泌体作为POF的治疗方案。

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Human Amniotic Epithelial Cell-Derived Exosomes Restore Ovarian Function by Transferring MicroRNAs against Apoptosis.

Premature ovarian failure (POF) is one of the most common complications among female patients with tumors treated with chemotherapy and requires advanced treatment strategies. Human amniotic epithelial cell (hAEC)-based therapy mediates tissue regeneration in a variety of diseases, and increasing evidence suggests that the therapeutic efficacy of hAECs mainly depends on paracrine action. This study aimed to identify exosomes derived from hAECs and explored the therapeutic potential in ovaries damaged by chemotherapy and the underlying molecular mechanism. hAEC-derived exosomes exhibited a cup- or sphere-shaped morphology with a mean diameter of 100 nm and were positive for Alix, CD63, and CD9. hAEC exosomes increased the number of follicles and improved ovarian function in POF mice. During the early stage of transplantation, hAEC exosomes significantly inhibited granulosa cell apoptosis, protected the ovarian vasculature from damage, and were involved in maintaining the number of primordial follicles in the injured ovaries. Enriched microRNAs (miRNAs) existed in hAEC exosomes, and target genes were enriched in phosphatidylinositol signaling and apoptosis pathways. Studies in vitro demonstrated that hAEC exosomes inhibited chemotherapy-induced granulosa cell apoptosis via transferring functional miRNAs, such as miR-1246. Our findings demonstrate that hAEC-derived exosomes have the potential to restore ovarian function in chemotherapy-induced POF mice by transferring miRNAs.