Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem ce...Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.展开更多
哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是一种高度保守的激酶,通过感知和整合细胞环境中的信号来调节生物生长、体内平衡,并在许多细胞的生长过程中发挥着关键作用。自噬是真核生物进化中高度保守的细胞内物质分...哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是一种高度保守的激酶,通过感知和整合细胞环境中的信号来调节生物生长、体内平衡,并在许多细胞的生长过程中发挥着关键作用。自噬是真核生物进化中高度保守的细胞内物质分解代谢物质循环过程。近年来,遗传学和功能研究表明,mTOR通过自噬途径在骨稳态调节中起着重要作用。作为PI3K/AKT/mTOR信号通路的核心环节,mTOR的激活或抑制对骨髓间充质干细胞/成骨细胞介导的骨形成、成脂分化,以及破骨细胞介导的骨吸收均具有正/负向调节作用。鉴于mTOR在自噬中对骨稳态的重要调控作用,该文就mTOR和自噬与骨稳态之间的联系进行综述,探讨mTOR在骨质疏松中的治疗潜力,以期望为骨质疏松症的治疗提供新的治疗靶点。展开更多
基金supported by the National Nature Science Foundation of China,No.81471308(to JL)the Innovative Leading Talents of Liaoning Province,No.XLYC1902031(to JL)+2 种基金Science and Technology Projects in Liaoning Province,No.2022-BS-238(to CH)Young Top Talents of Liaoning Province,No.XLYC1907009(to LW)Dalian Science and Technology Innovation Fund,No.2018J11CY025(to JL)。
文摘Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
文摘哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是一种高度保守的激酶,通过感知和整合细胞环境中的信号来调节生物生长、体内平衡,并在许多细胞的生长过程中发挥着关键作用。自噬是真核生物进化中高度保守的细胞内物质分解代谢物质循环过程。近年来,遗传学和功能研究表明,mTOR通过自噬途径在骨稳态调节中起着重要作用。作为PI3K/AKT/mTOR信号通路的核心环节,mTOR的激活或抑制对骨髓间充质干细胞/成骨细胞介导的骨形成、成脂分化,以及破骨细胞介导的骨吸收均具有正/负向调节作用。鉴于mTOR在自噬中对骨稳态的重要调控作用,该文就mTOR和自噬与骨稳态之间的联系进行综述,探讨mTOR在骨质疏松中的治疗潜力,以期望为骨质疏松症的治疗提供新的治疗靶点。
