卵巢早衰（POF）是指40歲前卵巢功能停止，伴有閉經(jīng)、血促性腺激素水平升高和雌激素水平降低和不孕癥，也是接受化療的女性腫瘤患者最常見的并發(fā)癥之一，需要采取先進的治療策略。最新研究報道了人羊膜上皮細胞（hAEC）衍生的外泌體可以通過轉移microRNA(miRNA)抵抗細胞凋亡，從而實現(xiàn)卵巢功能的恢復。相關研究結果發(fā)表在Molecular Therapy-Nucleic Acids雜志上。

人羊膜上皮細胞在治療多種疾病中顯示出介導組織再生的能力，越來越多的證據(jù)表明hAEC的治療效果主要取決于旁分泌作用。該研究鑒定了源自hAEC的外泌體，并研究了hAEC源外泌體對化療誘導的POF小鼠中卵泡發(fā)育和卵巢功能的影響。研究結果顯示，hAEC外泌體可顯著增加POF小鼠的卵泡數(shù)量和改善卵巢功能。在移植早期，hAEC外泌體顯著抑制顆粒細胞凋亡，保護卵巢脈管系統(tǒng)免受損傷，并參與維持受損卵巢中原始卵泡的數(shù)量。進一步發(fā)現(xiàn)富集的miRNA存在于hAEC外泌體中，因此，hAEC衍生的外泌體具有通過轉移miRNA實現(xiàn)恢復化療誘導的POF小鼠卵巢功能的潛力。

該項研究表明，hAECs改善卵巢功能可能源于外泌體的作用，提示未來或可利用hAEC源外泌體作為POF的治療方案。

推薦閱讀原文：

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.