Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions.
Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions.
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源自人诱导多能干细胞源性神经祖细胞的外泌体在缺血条件下保护神经元功能
DOI：
10.4103/1673-5374.308665
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发表时间：
2021-10
影响因子：
6.1
通讯作者：
Hu XY
中科院分区：
文献类型：
--
作者：
Li WY;Zhu QB;Jin LY;Yang Y;Xu XY;Hu XY
与其他干细胞相比，人诱导多能干细胞来源的神经前体细胞（iPSC-NPCs）在形态学和免疫组织化学上更接近于皮层神经元。因此，它们具有促进神经元存活和生长以及减轻星形胶质细胞增殖的更大潜力。干细胞外泌体和干细胞本身的移植都被证明可以有效地修复神经损伤。然而，还没有关于来源于iPSC-NPC的外泌体对氧和葡萄糖剥夺的神经元的保护作用的研究。在这项研究中，我们通过在95%N2和5%CO2的气氛中培养神经元1小时，然后用iPSC-NPC衍生的外泌体处理它们30分钟，在大鼠胚胎皮层神经元中建立了氧-葡萄糖剥夺模型。我们的研究结果表明，iPSC-NPC衍生的外泌体增加了缺氧和缺糖神经元的存活率以及培养基中脑源性神经营养因子的水平。此外，它还减弱了氧气和葡萄糖剥夺引起的PTEN/AKT信号通路以及神经元中突触可塑性相关蛋白表达的变化。此外，它增加了缺氧和缺糖神经元中最长神经突的长度。这些发现验证了来自iPSC-NPC的外泌体通过调节PTEN/AKT信号通路和神经突生长对氧和葡萄糖剥夺的神经元表现出神经保护作用的假设。本研究于2019年10月10日获得浙江大学医学院附属邵逸夫医院动物伦理委员会批准（批准号：SRRSH 20191010）。
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 iPSC-NPCs 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.
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影响因子：
3.3
作者：
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