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用于工程纳米材料安全性筛选的基于细胞的细胞毒性测定:脂肪来源的基质细胞暴露于二氧化钛纳米颗粒。

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

作者信息

Xu Yan, Hadjiargyrou M, Rafailovich Miriam, Mironava Tatsiana

机构信息

Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY, USA.

Department of Life Sciences, New York Institute of Technology, Old Westbury, NY, USA.

出版信息

J Nanobiotechnology. 2017 Jul 11;15(1):50. doi: 10.1186/s12951-017-0285-2.

Abstract

BACKGROUND

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).

RESULTS

Herein, we report that titanium dioxide (TiO) 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 TiO 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.

CONCLUSIONS

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.

摘要

背景

纳米材料产量的不断增加需要对其潜在毒性进行快速且恰当的评估。因此,有必要开发新的体外检测方法,这些方法要具有成本效益,并能更快地筛选工程纳米材料(ENMs)。

结果

在此,我们报告二氧化钛(TiO)纳米颗粒(NPs)能够在被诸如测量增殖、活性氧(ROS)和乳酸脱氢酶(LDH)水平等标准检测方法评定为安全的浓度下,对脂肪来源的间充质干细胞(ADSCs)造成损伤。具体而言,我们证明了低浓度的TiO NPs,在这些浓度下细胞LDH、ROS或增殖情况未受影响,但却诱导了ADSCs分泌功能和分化能力的改变。这两种功能对于ADSCs在伤口愈合、能量消耗和新陈代谢中至关重要,在体内具有严重的健康影响。

结论

我们证明基于特定细胞功能的细胞毒性检测方法具有更高的灵敏度,并能揭示传统ROS、LDH和增殖检测方法未检测到的由ENMs诱导的损伤。为了对ENMs进行恰当的毒理学评估,标准的ROS、LDH和增殖检测方法应与研究特定细胞类型相关细胞功能的检测方法相结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8052/5504822/92b570ebfdbe/12951_2017_285_Fig1_HTML.jpg

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