MSCs治疗早发性卵巢功能不全的免疫调节作用及PGE2/EP潜在机制

Immunoregulation of MSCs in the treatment with premature ovarian insufficiency and potential mechanisms of PGE2/EP

早发性卵巢功能不全(POI)严重影响女性的生殖健康。其发病机制与药物、免疫和遗传等多因素相关,而T细胞免疫失衡是自身免疫性POI和炎症性卵巢损伤的重要致病机制,目前采用的雌激素替代治疗虽能缓解POI部分临床症状,但缺乏有效修复卵巢功能的措施。近年的研究表明,间充质干细胞(MSCs)移植已成为改善POI临床症状、恢复卵巢组织结构与功能及垂体-性腺轴激素平衡的新方法,颇具临床应用前景。前列腺素E2(PGE2)通过与其受体(receptor, EP)结合,不但参与多种免疫细胞和炎症反应调节,还可影响血流量、分泌、生殖细胞和MSCs的功能和发育。PGE2可能与其他炎症因子相似,是免疫授权调节MSCs功能活性的关键分子。本文综述了MSCs治疗POI的作用和机制,重点涉及T细胞免疫与PGE2/EP调节机制的研究进展。

Premature ovarian insufficiency(POI)seriously affects female reproductive health.The pathogens are complex and include drugs,immunity,genetics and others.The imbalance of T cells immunity is an important pathogenesis of autoimmune POI and inflammatory ovarian injury.In clinic,estrogen replacement therapy can relieve some clinical symptoms in POI patients.However,there is still a lack of effective treatment to repair ovarian function.Recent studies have shown that transplantation of mesenchymal stem cells(MSCs)has become a promising new method to improve clinical symptoms,to restore ovarian tissue structure and function,and to balance the hormones of pituitary-gonadal axis of POI patients.Prostaglandin E2(PGE2),by binding to its receptor EP,not only regulates a variety of immune cells and inflammatory reaction,but also affects blood flow,secretion,biological characteristics of reproductive cells and MSCs.PGE2 may be a key molecule immunologically authorized to regulate the functional activity of MSCs,similar to other inflammatory factors.In this review,we analyzed the data published in the current papers and demonstrated the effects and mechanism of MSCs in the treatment of POI,specially focusing on related T cell immunity and PGE2/EP regulation.