人脐带间充质干细胞来源的microvesicles对AD的治疗作用及其机制研究

β淀粉样蛋白(Aβ)导致的神经毒性作用以及小胶质细胞激活导致的免疫炎症反应是AD的重要发病机制。减轻Aβ神经毒性作用导致的氧化应激损伤和神经丢失，以及调节小胶质细胞免疫炎症反应成为治疗AD的重要方向。最新研究报道间充质干细胞（MSCs）可以分泌微泡（MVs），它能够模仿MSCs的功能，这为AD的“无细胞”治疗带来了新的前景。有研究表明炎症因子刺激间充质干细胞可以使其分泌的MVs中TGFβ的含量明显提高。在此基础上，我们利用AD转基因小鼠为模型，探讨人脐带MSCs来源的MVs（HUMSC-MVs）或炎症因子刺激HUMSC所分泌的MVs（S-HUMSC-MVs）移植对AD小鼠认知功能、Aβ沉积、氧化应激损伤、突触及神经生成和小胶质细胞免疫炎症反应的影响，并通过调控TGFβ的表达，探讨小胶质细胞替代激活（M2）的细胞分子机制，从而为AD的治疗提供了新的安全有效的方法。

β -amyloid (Aβ) neurotoxicity and immuno-inflammation induced by activation of microglia is important in the pathogenesis of AD. Recent therapy focuses on reducing oxidative stress and nerve loss, as well as regulating immuno-inflammation of microglia. Mesenchymal stem cells (MSCs) can secrete microvesicles (MVs), which can mimic the function of MSCs. MVs opens new prospects for AD "cell-free" therapy. Studies have shown that inducing inflammatory setting on MSCs can make higer TGFβ secretion levels of MVs. On this basis, we infuse the human umbilical cord MSCs derived MVs (HUMSC-MVs) or inflammatory cytokines stimulated HUMSC MVs (S-HUMSC-MVs) into AD mice model. We study the effect of HUMSC-MVs or S-HUMSC-MVs on behavior, Aβ deposition, oxidative stress, neurogenesis and immuno-inflammation. We explore cellular and molecular mechanisms of alternative activation of microglia (M2) by regulating the expression of TGFβ. MVs infusion is new and safe therapy for AD.