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

M. Hadjiargyrou,Miriam Rafailovich,Tatsiana Mironava,Yan Xu

doi:10.1186/s12951-017-0285-2

M. Hadjiargyrou, Miriam Rafailovich + Show 2 more

Open Access

https://doi.org/10.1186/s12951-017-0285-2

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Abstract

BackgroundIncreasing 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).ResultsHerein, 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.ConclusionsWe 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.

Highlights

Increasing production of nanomaterials requires fast and proper assessment of its potential toxicity
There are several different cell types that are targeted by engineered nanomaterials (ENMs) through common routes of exposure: lung epithelium, skin fibroblasts and adipocytes, gastrointestinal tract epithelia, and cells belonging to the reticuloendothelial system such as macrophages [4, 6]
Evaluation of ENMs cytotoxicity based on delivered doses should help to eliminate this difference and enable efficient and reliable in vitro screening methods

Summary

Introduction

Increasing production of nanomaterials requires fast and proper assessment of its potential toxicity. To be able to properly screen and predict the potential toxicity of ENMs, sensitive and reliable in vitro assays need to be developed as soon as possible [1,2,3] Such assays should be relevant to a real life exposure scenario, be cost effective to allow for massive ENMs screening, and measure common modes of cellular responses [4]. There are several different cell types that are targeted by ENMs through common routes of exposure: lung epithelium, skin fibroblasts and adipocytes, gastrointestinal tract epithelia, and cells belonging to the reticuloendothelial system such as macrophages [4, 6] Since all of these cells have unique functions in tissues and organs, there is no universal strategy for ENMs hazard assessment.

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