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Cell-based cytotoxicity assays for engineered nanomaterials safety screening: exposure of adipose derived stromal cells to titanium dioxide nanoparticles

机译:用于工程纳米材料安全筛选的基于细胞的细胞毒性测定:脂肪基质细胞暴露于二氧化钛纳米颗粒

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Increasing production of nanomaterials requires fast and proper assessment of its potential toxicity. Therefore, there is a need to develop new assays that can be performed in vitro, be cost effective, and allow faster screening of engineered nanomaterials (ENMs). Herein, we report that titanium dioxide (TiO2) nanoparticles (NPs) can induce damage to adipose derived stromal cells (ADSCs) at concentrations which are rated as safe by standard assays such as measuring proliferation, reactive oxygen species (ROS), and lactate dehydrogenase (LDH) levels. Specifically, we demonstrated that low concentrations of TiO2 NPs, at which cellular LDH, ROS, or proliferation profiles were not affected, induced changes in the ADSCs secretory function and differentiation capability. These two functions are essential for ADSCs in wound healing, energy expenditure, and metabolism with serious health implications in vivo. We demonstrated that cytotoxicity assays based on specialized cell functions exhibit greater sensitivity and reveal damage induced by ENMs that was not otherwise detected by traditional ROS, LDH, and proliferation assays. For proper toxicological assessment of ENMs standard ROS, LDH, and proliferation assays should be combined with assays that investigate cellular functions relevant to the specific cell type.
机译:纳米材料产量的增加要求对其潜在毒性进行快速而适当的评估。因此,需要开发可以在体外进行,具有成本效益并且允许更快筛选工程纳米材料(ENM)的新测定法。在本文中,我们报道了二氧化钛(TiO2)纳米颗粒(NPs)可以诱导脂肪衍生的基质细胞(ADSCs)受到一定程度的破坏,这些浓度在通过标准测定(如测量增殖,活性氧(ROS)和乳酸脱氢酶)被评为安全(LDH)级别。具体来说,我们证明了低浓度的TiO2 NPs不会影响细胞的LDH,ROS或增殖曲线,从而引起ADSC分泌功能和分化能力的改变。这两种功能对于ADSC在伤口愈合,能量消耗和新陈代谢方面至关重要,在体内对健康有严重影响。我们证明了基于专门细胞功能的细胞毒性试验显示出更高的敏感性,并揭示了由ENM诱导的损伤,而传统的ROS,LDH和增殖试验则无法检测到这种损伤。为了对ENM进行适当的毒理学评估,应将标准ROS,LDH和增殖测定与研究与特定细胞类型相关的细胞功能的测定相结合。

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