Intracellular Reactive Oxygen Species Mediate the Therapeutic Effect of Induced Pluripotent Stem Cells for Acute Kidney Injury
Intracellular Reactive Oxygen Species Mediate the Therapeutic Effect of Induced Pluripotent Stem Cells for Acute Kidney Injury
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DOI：
10.1155/2020/1609638
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发表时间：
2020-03
影响因子：
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通讯作者：
Shun Wang;Xiaoyu Tian;Yijun Li;R. Xue;Haochen Guan;Meng Lu;Huijun Xu;Zhibin Ye;Sifen chen;Meng Xiang
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文献类型：
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作者：
Shun Wang;Xiaoyu Tian;Yijun Li;R. Xue;Haochen Guan;Meng Lu;Huijun Xu;Zhibin Ye;Sifen chen;Meng Xiang
目的急性肾损伤（AKI）的治疗具有挑战性。诱导多能干细胞（iPSCs）具有巨大的治疗潜力。本研究旨在确定iPSCs是否减弱AKI和活性氧（ROS）的作用。结果在小鼠肾缺血再灌注损伤（IRI）后2 h静脉注射等基因iPSCs。将这些细胞选择性地输送到缺血/再灌注损伤的肾脏中，可以减少肾脏ROS和炎症细胞因子，改善肾脏功能和形态。在给药前用ROS抑制剂预处理细胞可减少iPSC的植入，并消除iPSC的保护作用。相比之下，过氧化氢预处理iPSC可增加iPSC的植入和治疗效果。虽然静脉给药的iPSCs运输到IRI肾，细胞没有分化成近端或远端小管上皮细胞。在体外实验中，通过对ipsc进行ROS预处理，ipsc释放的物质促进肾上皮细胞增殖和减少细胞凋亡的能力增强。此外，用ROS抑制剂预处理iPSCs具有相反的效果。同样，中等浓度的ROS增加，而ROS抑制剂降低iPSC的迁移率、与细胞外基质的粘附以及线粒体代谢。创新与结论。ipsc主要通过ipsc释放的物质减轻肾缺血再灌注损伤。诱导多能干细胞的治疗效果、线粒体代谢、移动性和肾脏运输均依赖于活性氧。
Aims Treatment for acute kidney injury (AKI) is challenging. Induced pluripotent stem cells (iPSCs) have great therapeutic potential. This study sought to determine whether iPSCs attenuate AKI and the role of reactive oxygen species (ROS). Results We intravenously injected isogenic iPSCs into mice 2 h after renal ischemia-reperfusion injury (IRI). The cells were selectively trafficked to ischemia/reperfusion-injured kidney where they decreased kidney ROS and inflammatory cytokines and improved kidney function and morphology. Pretreating the cells with ROS inhibitors before administration decreased iPSC engraftment and abolished the protective effect of iPSCs. In contrast, pretreating iPSCs with hydrogen peroxide increased iPSC engraftment and therapeutic effect. Although the intravenously administered iPSCs trafficked to the IRI kidney, the cells did not differentiate into proximal or distal tubular epithelial cells. In vitro, the capabilities of the iPSC-released substances to promote proliferation and decrease apoptosis of renal epithelial cells were increased by ROS pretreatment of iPSCs. Moreover, pretreatment of the iPSCs with ROS inhibitor had the opposite effect. Similarly, moderate concentrations of ROS increased while ROS inhibitors decreased iPSC mobility, adhesion to the extracellular matrix, and mitochondrial metabolism. Innovation and Conclusion. iPSCs decreased renal ischemia/reperfusion injury mainly through iPSC-released substances. The therapeutic effect, mitochondrial metabolism, mobility, and kidney trafficking of iPSCs were ROS dependent.