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
目的探讨急性脑梗塞(ACI)患者血清N末端B型利钠肽原(NT-proBNP)/B型利钠肽(BNP)、肌酸激酶同工酶(CK-MB)、D-二聚体(D-D)水平变化及对并发脑心综合征(CCS)的预测价值。方法纳入2020年8月至2023年8月间合肥市第八人民医院收治的ACI患者92...目的探讨急性脑梗塞(ACI)患者血清N末端B型利钠肽原(NT-proBNP)/B型利钠肽(BNP)、肌酸激酶同工酶(CK-MB)、D-二聚体(D-D)水平变化及对并发脑心综合征(CCS)的预测价值。方法纳入2020年8月至2023年8月间合肥市第八人民医院收治的ACI患者92例,根据是否并发CCS分为ACI组58例和CCS组34例,另选取同时期本院招募的健康志愿者50名为对照组。采集各组患者血液,检测NT-proBNP、BNP、CK-MB、D-D水平并计算NT-proBNP/BNP值;统计分析上述指标与ACI患者并发CCS的关系和预测价值。结果各组的NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D水平均有CCS组>ACI组>对照组,差异具有统计学意义(P<0.05);NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D、吸烟、嗜酒、高血压、冠心病、糖尿病、高血脂为发生ACI的危险因素,NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D、吸烟、嗜酒为ACI并发CCS的危险因素(P<0.05);NT-proBNP/BNP、CK-MB、D-D联合诊断ACI并发CCS的曲线下面积(Area under curve,AUC)最大,优于单一检测(P<0.05);NT-proBNP、BNP、NT-proBNP/BNP、CK-MB均与D-D水平正相关(P<0.05)。结论血清NT-proBNP/BNP、CK-MB、D-D水平的升高与ACI患者并发CCS相关,对ACI患者并发CSS均具有预测价值。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.
文摘目的探讨急性脑梗塞(ACI)患者血清N末端B型利钠肽原(NT-proBNP)/B型利钠肽(BNP)、肌酸激酶同工酶(CK-MB)、D-二聚体(D-D)水平变化及对并发脑心综合征(CCS)的预测价值。方法纳入2020年8月至2023年8月间合肥市第八人民医院收治的ACI患者92例,根据是否并发CCS分为ACI组58例和CCS组34例,另选取同时期本院招募的健康志愿者50名为对照组。采集各组患者血液,检测NT-proBNP、BNP、CK-MB、D-D水平并计算NT-proBNP/BNP值;统计分析上述指标与ACI患者并发CCS的关系和预测价值。结果各组的NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D水平均有CCS组>ACI组>对照组,差异具有统计学意义(P<0.05);NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D、吸烟、嗜酒、高血压、冠心病、糖尿病、高血脂为发生ACI的危险因素,NT-proBNP、BNP、NT-proBNP/BNP、CK-MB、D-D、吸烟、嗜酒为ACI并发CCS的危险因素(P<0.05);NT-proBNP/BNP、CK-MB、D-D联合诊断ACI并发CCS的曲线下面积(Area under curve,AUC)最大,优于单一检测(P<0.05);NT-proBNP、BNP、NT-proBNP/BNP、CK-MB均与D-D水平正相关(P<0.05)。结论血清NT-proBNP/BNP、CK-MB、D-D水平的升高与ACI患者并发CCS相关,对ACI患者并发CSS均具有预测价值。
