羊膜间充质干细胞治疗免疫性卵巢早衰中前列腺素E2的免疫授权机制研究

作为调节器和感受器，间充质干细胞（MSC）释放前列腺素E2（PGE2）激活免疫细胞EP受体发挥免疫抑制和促损伤修复的治疗作用；同时PGE2也能增强MSC释放抗炎因子。我们发现表达EP受体的人羊膜MSC(AMSC)治疗卵巢早衰（POF）涉及改善微环境、调节免疫平衡、促卵巢上皮细胞和卵泡发育的机制。本项目拟采用共培养、流式细胞术、超滤、高通量测序、Western blot、活体成像和病理检查等，以AMSC治疗免疫性POF的T细胞免疫调节作用为基础，在一定PGE2和炎症因子共存、激动和阻断EP条件下，重点研究AMSCs的外泌体、PGE2、炎症与卵泡发育相关因子分泌、T细胞免疫调节及生物学特征变化，首先探讨PGE2/EP途径激活在AMSC免疫授权中的作用和确切机制，为准确调控AMSC免疫调节和再生修复功能，合理应用免疫抑制增强型AMSC治疗POF提供重要的决策依据和技术基础。

As an immune inflammatory regulators and receptors, mesenchymal stem cells (MSC) secretes prostaglandin E2 (PGE2) to activate the EP receptor of immune cells for playing the therapeutic role of immunosuppression and injury repair. We found that the therapeutic effects of human amniotic MSC (AMSC) expressing EP receptor involves improving the mechanisms of improve microenvironment， regulation of immune balance and promoting ovarian epithelial and follicular development for premature ovarian failure (POF). In this project, these methods all will be used, such as co-culture, flow cytometry assay, ultrafiltration, high-throughput sequencing, western blot, in vivo imaging and pathological examination and so on. Based on the T cells immunomodulatory effect of AMSC in the treatment of autoimmune POF, and under the coexisting conditions of a certain PGE2 level and inflammatory factors, agitating and blocking EP, the study will focuse on the function changes of AMSCs secreting exosome, PGE2, inflammatory cytokine and related factors of follicle development, and T cell immune regulation, the basic biological characteristics. The role and exact mechanism of PGE2/EP pathway activation were first investigated on AMSC immunization authorization. These results will provide important decision basis and technical basis for the accurate regulation of AMSC immune regulation and regenerative repair function, and the rational application of immunosuppressive enhanced AMSC in the treatment of POF.