利用人体诱导多能干细胞衍生的耳祖细胞建立人体内耳氧化应激体外模型

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Minjin Jeong, Sho Kurihara, Konstantina M Stankovic
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引用次数: 0

摘要

负责听觉(耳蜗)和平衡(前庭系统)的内耳器官由于其感音细胞的高代谢需求而容易受到氧化应激的影响。氧化应激引起的这些细胞损伤可导致听力损失或前庭功能障碍,但由于动物模型的局限性和获取活体人体内耳组织的挑战,其确切机制仍不清楚。因此,我们利用从人类诱导多能干细胞(hiPSCs)中提取的耳祖细胞(OPCs),开发了一种产前人类内耳体外氧化应激模型。将 OPCs、hiPSCs 和 HeLa 细胞暴露于过氧化氢或诱导氧化应激的耳毒性药物(庆大霉素和顺铂)中,以评估随后的细胞活力、细胞死亡、活性氧(ROS)产生、线粒体活性和细胞凋亡(caspase 3/7 活性)。暴露后观察到 OPC 细胞活力呈剂量依赖性降低,这表明它们很容易受到氧化应激的影响。值得注意的是,庆大霉素暴露会诱导 ROS 生成和 OPC 细胞死亡,但不会诱导 hiPSCs 或 HeLa 细胞死亡。这种基于 OPC 的人体模型有效地模拟了人内耳的氧化应激条件,可用于模拟妊娠早期耳毒性的影响或评估预防细胞毒性的疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells.

The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise mechanisms remain unclear due to the limitations of animal models and challenges of obtaining living human inner ear tissue. Therefore, we developed an in vitro oxidative stress model of the pre-natal human inner ear using otic progenitor cells (OPCs) derived from human-induced pluripotent stem cells (hiPSCs). OPCs, hiPSCs, and HeLa cells were exposed to hydrogen peroxide or ototoxic drugs (gentamicin and cisplatin) that induce oxidative stress to evaluate subsequent cell viability, cell death, reactive oxygen species (ROS) production, mitochondrial activity, and apoptosis (caspase 3/7 activity). Dose-dependent reductions in OPC cell viability were observed post-exposure, demonstrating their vulnerability to oxidative stress. Notably, gentamicin exposure induced ROS production and cell death in OPCs, but not hiPSCs or HeLa cells. This OPC-based human model effectively simulates oxidative stress conditions in the human inner ear and may be useful for modeling the impact of ototoxicity during early pregnancy or evaluating therapies to prevent cytotoxicity.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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