Advances in the use of nanoparticles (NPs) has created promising progress in biotechnology and consumer-care based industry. This has created an increasing need for testing their safety and toxicity profiles. Hence, efforts to understand the cellular responses towards nanomaterials are needed. However, current methods using animal and cancer-derived cell lines raise questions on physiological relevance. In this aspect, in the current study, we investigated the use of pluripotent human embryonic stem cell- (hESCs) derived fibroblasts (hESC-Fib) as a closer representative of the in vivo response as well as to encourage the 3Rs (replacement, reduction and refinement) concept for evaluating the cytotoxic and genotoxic effects of zinc oxide (ZnO), titanium dioxide (TiO₂) and silicon-dioxide (SiO₂) NPs. Cytotoxicity assays demonstrated that the adverse effects of respective NPs were observed in hESC-Fib beyond concentrations of 200 µg/mL (SiO₂ NPs), 30 µg/mL (TiO₂ NPs) and 20 µg/mL (ZnO NPs). Flow cytometry results correlated with increased apoptosis upon increase in NP concentration. Subsequently, scratch wound assays showed ZnO (10 µg/mL) and TiO₂ (20 µg/mL) NPs inhibit the rate of wound coverage. DNA damage assays confirmed TiO₂ and ZnO NPs are genotoxic. In summary, hESC-Fib could be used as an alternative platform to understand toxicity profiles of metal oxide NPs.

中文翻译：

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金属氧化物纳米粒子在人类多能干细胞衍生成纤维细胞中的细胞毒性和遗传毒性

纳米粒子（NPs）的使用进展已在生物技术和基于消费者护理的行业中创造了可喜的进步。因此，越来越需要测试其安全性和毒性。因此，需要努力了解细胞对纳米材料的反应。然而，当前使用动物和癌症来源的细胞系的方法引起了关于生理相关性的问题。在这一方面，在当前研究中，我们研究了使用多能人类胚胎干细胞（hESCs）成纤维细胞（hESC-Fib）作为体内反应的更接近代表以及鼓励3R（替代，减少和精制）概念，用于评估氧化锌（ZnO），二氧化钛（TiO ₂）和二氧化硅（SiO ₂）的细胞毒性和遗传毒性）NP。细胞毒性试验表明，在浓度超过200 µg / mL（SiO ₂ NPs），30 µg / mL（TiO ₂ NPs）和20 µg / mL（ZnO NPs）的hESC-Fib中，观察到了相应的NPs的不良反应。流式细胞术结果与NP浓度增加时细胞凋亡增加有关。随后，刮伤试验显示ZnO（10 µg / mL）和TiO ₂（20 µg / mL）NPs抑制伤口覆盖率。DNA损伤分析证实了TiO ₂和ZnO NP具有遗传毒性。总之，hESC-Fib可以用作了解金属氧化物NPs毒性概况的替代平台。