Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions  

作　　者：Wen-Yu Li Qiong-Bin Zhu Lu-Ya Jin Yi Yang Xiao-Yan Xu Xing-Yue Hu 

机构地区：[1]Department of Neurology,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou,Zhejiang Province,China [2]Brain Research Institute,Zhejiang University,Hangzhou,Zhejiang Province,China

出　　处：《Neural Regeneration Research》2021年第10期2064-2070,共7页中国神经再生研究（英文版）

基　　金：This work was supported by the Foundation of Zhejiang Provincial Basic Public Welfare Research Program of China,No.LGF19H090024(to XYX);the Natural Science Foundation of Zhejiang Province of China,No.LY17H090006(to WYL);National Natural Science foundation of China,No.81901073(to QBZ).

摘　　要：Compared with other stem cells,human induced pluripotent stem cells-derived neural progenitor cells(iPSC-NPCs)are more similar to cortical neurons in morphology and immunohistochemistry.Thus,they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes.Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury.However,there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons.In this study,we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95%N2 and 5%CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes.Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen-and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium.Additionally,it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons.Further,it increased the length of the longest neurite in the oxygen-and glucose-deprived neurons.These findings validate the hypothesis that exosomes from iPSCNPCs exhibit a neuroprotective effect on oxygen-and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth.This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,China(approval No.SRRSH20191010)on October 10,2019.

关 键 词：AKT cortical neurons EXOSOME ISCHEMIA neural progenitor cells neuronal protection oxygen and glucose deprivation pluripotent stem cells PTEN signaling pathway 

分 类 号：R338[医药卫生—人体生理学]