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首页> 外文期刊>Stem cells international >In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons
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In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons

机译:用人神经母细胞瘤细胞和诱导多能干细胞衍生神经元的体外氧 - 葡萄糖剥夺诱导的卒中模型

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Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced pluripotent stem cells (hiPSCs) were differentiated into neurons, cultured under OGD conditions (1% O2) for 24?h, and subjected to a reperfusion period for 24 or 72?h. After OGD, ASCs were cocultured with neurons on inserts for 24 or 72?h to study the neuroprotective potential of ASCs. The effect of OGD and ASC coculture on the viability, apoptosis, and proliferation of and axonal damage to neuronal cells was studied. The results showed that OGD conditions induced cytotoxicity and apoptosis of SH-SY5Y- and hiPSC-derived neurons, although more severe damage was detected in SH-SY5Y-derived neurons than in hiPSC-derived neurons. Coculture with ASCs was protective for neurons, as the number of dead ASC-cocultured neurons was lower than that of control cells, and coculture increased the proliferation of both cell types. To conclude, we developed in vitro human cell-based stroke models in SH-SY5Y- and hiPSC-derived neurons. This was the first time hiPSCs were used to model stroke in vitro. Since OGD had different effects on the studied cell types, this study highlights the importance of using several cell types in in vitro studies to confirm the outcomes of the study. Here, ASCs exerted a neuroprotective effect by increasing the proliferation and decreasing the death of SH-SY5Y- and hiPSC-derived neurons after OGD.
机译:中风是一种毁灭性的神经疾病和死亡率和残疾的主要原因之一。为了了解中风的细胞和分子机制并发展新的治疗方法,使用氧葡萄糖剥夺(OGD)条件建立两种不同的体外人细胞的中风模型。此外,研究了脂肪干细胞(ASCS)对OGD诱导损伤的影响。在本研究中,SH-SY5Y人类神经母细胞瘤细胞和人诱导的多能干细胞(HIPSCS)分化为神经元,在OGD条件下(1%O 2)培养24℃,并进行再灌注时间24或72? H。在OGD后,ASC在插入物上与神经元进行聚集,持续24或72Ω·h以研究ASCS的神经保护潜力。研究了OGD和ASC共gultupt对神经元细胞的活力,凋亡和增殖和轴突损伤的影响。结果表明,OGD条件诱导了SH-SY5Y-和HIPSC衍生神经元的细胞毒性和凋亡,但在SH-SY5Y衍生的神经元中检测到比HIPSC衍生的神经元更严重的损伤。与ASCS的共培养是神经元的保护性,因为死亡的ASC-CoCultuce神经元的数量低于对照细胞的数量,并且共培养增加了两种细胞类型的增殖。为了得出结论,在SH-SY5Y-和HIPSC衍生的神经元中开发了体外人体细胞的中风模型。这是第一次HIPSCS用于在体外模拟中风。由于OGD对所研究的细胞类型产生不同的影响,因此该研究突出了在体外研究中使用几种细胞类型以确认研究结果的重要性。在这里,ASCS通过增加OGD后的增殖和降低SH-SY5Y-和HIPSC衍生的神经元的死亡来施加神经保护作用。

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