期刊文献

hRPE cells derived from induced pluripotent stem cells are more sensitive to oxidative stress than ARPE-19 cells 收藏

衍生自诱导多能干细胞的hRPE细胞对氧化应激比对ARPE-19细胞更敏感
原文求助 发布源
作者
AudreyVoisin[a][b];ChristelleMonville[c][d];AlexandraPlancheron[c][d][e];AnaïsBalbous[a][f];AfsanehGaillard[a][b];NicolasLeveziel[a][f];
作者单位
[a]INSERM, U1084, Experimental and Clinical Neuroscience Laboratory, Cellular Therapies in Brain Diseases Group, Poitiers, F-86022, France[b]University of Poitiers, Experimental and Clinical Neuroscience Laboratory, Cellular Therapies in Brain Diseases Group, Poitiers, F-86073, France[c]INSERM, UMR861, I-Stem, AFM, Genopole Campus 1, Corbeil Essonnes, F- 91100, France[d]UEVE, UMR861, I-Stem, AFM, Genopole Campus 1, Corbeil Essonnes, F- 91100, France[e]CECS, UMR861, I-Stem, AFM, Genopole Campus 1, Corbeil Essonnes, F- 91100, France[f]CHU of Poitiers, Poitiers, F-86021, France
关键词
Age-related macular degeneration; Induced pluripotent stem cells; Disease modeling; Oxidative stress; ARPE-19 cells;
关键词译文
年龄相关性黄斑变性;诱导多能干细胞;疾病模型;氧化应激; ARPE-19细胞;
发布日期
1 December 2018
页码
76-86
DOI
10.1016/j.exer.2018.07.017
来源信息
Experimental Eye Research ISSN：0014-4835, 2018年, 177卷, 76-86页
摘要
The ARPE-19 cell line is currently used as an in vitro model for retinal diseases such as age-related degeneration (AMD). However, several studies have pointed out morphological and genetic differences between ARPE-19 cells and human fetal or adult retinal pigment epithelial (hRPE) cells. This study aims to compare ARPE-19 cells to hRPE cells derived from human induced pluripotent stem cells (hiPSCs) in both normal and oxidative stress conditions induced by Fe-NTA treatment. Indeed, oxidative stress is an essential contributing factor in AMD. hiPSC obtained from peripheral venous blood samples or fibroblasts of individuals aged over 60 years were first reprogrammed to hiPSC and then differentiated into RPE cells. In contrast to ARPE-19 cells, hiPSC-RPE cells expressed β-galactosidase activity, suggesting that only the latter display signs of senescence. Treatment with 10 mM of FeNTA induced a higher reactive oxygen species (ROS) production and increased cell death in hiPSC-RPE cells compared to ARPE-19 cells. Moreover, morphological analysis and Annexin V and Propidium iodide (PI) test suggested a necrotic cell death pattern induced by treatment in hiPSC-RPE cells that is not observed in ARPE-19 cells. Taken as a whole, our findings suggest that hiPSC-RPE cells are more sensitive to oxidative stress than ARPE-19 cells.
摘要译文
ARPE-19细胞系目前用作视网膜疾病（例如年龄相关性变性（AMD））的体外模型。然而，一些研究指出了ARPE-19细胞与人胎儿或成人视网膜色素上皮细胞（hRPE）之间的形态和遗传差异。本研究旨在将ARPE-19细胞与源自人诱导多能干细胞（hiPSCs）的hRPE细胞在Fe-NTA处理诱导的正常和氧化应激条件下进行比较。实际上，氧化应激是AMD的重要因素。从外周静脉血样品或60岁以上个体的成纤维细胞获得的hiPSC首先重编程为hiPSC，然后分化成RPE细胞。与ARPE-19细胞相反，hiPSC-RPE细胞表达β-半乳糖苷酶活性，表明只有后者显示衰老迹象。与ARPE-19细胞相比，用10mM FeNTA处理诱导hiPSC-RPE细胞中更高的活性氧（ROS）产生和增加的细胞死亡。此外，形态学分析和膜联蛋白V和碘化丙啶（PI）试验表明在HEPSC-RPE细胞中通过处理诱导的坏死细胞死亡模式在ARPE-19细胞中未观察到。总的来说，我们的研究结果表明，hiPSC-RPE细胞对氧化应激的敏感性高于ARPE-19细胞。
AudreyVoisin[a][b];ChristelleMonville[c][d];AlexandraPlancheron[c][d][e];AnaïsBalbous[a][f];AfsanehGaillard[a][b];NicolasLeveziel[a][f];. hRPE cells derived from induced pluripotent stem cells are more sensitive to oxidative stress than ARPE-19 cells[J]. Experimental Eye Research, 2018,177: 76-86