Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure

Meindl, Claudia; Öhlinger, Kristin; Zrim, Verena; Steinkogler, Thomas; Frőhlich, Eleonore

doi:10.3390/nano11030606

Cited by 24 publications

(21 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In tricultures, no effect of NM-300K was seen on DNA damage in EA.hy926 cells. This might be linked to the potential uptake of NMs by the dTHP-1 cells as previously shown [ 75 , 81 ] making the material less available for cell exposure. One can even speculate if the exposed THP1 cells trigger an inflammatory reaction that can promote DNA repair [ 82 ].…”

Section: Discussionmentioning

confidence: 95%

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

et al. 2022

View full text Add to dashboard Cite

Advanced in vitro models are needed to support next-generation risk assessment (NGRA), moving from hazard assessment based mainly on animal studies to the application of new alternative methods (NAMs). Advanced models must be tested for hazard assessment of nanomaterials (NMs). The aim of this study was to perform an interlaboratory trial across two laboratories to test the robustness of and optimize a 3D lung model of human epithelial A549 cells cultivated at the air–liquid interface (ALI). Potential change in sensitivity in hazard identification when adding complexity, going from monocultures to co- and tricultures, was tested by including human endothelial cells EA.hy926 and differentiated monocytes dTHP-1. All models were exposed to NM-300K in an aerosol exposure system (VITROCELL® cloud-chamber). Cyto- and genotoxicity were measured by AlamarBlue and comet assay. Cellular uptake was investigated with transmission electron microscopy. The models were characterized by confocal microscopy and barrier function tested. We demonstrated that this advanced lung model is applicable for hazard assessment of NMs. The results point to a change in sensitivity of the model by adding complexity and to the importance of detailed protocols for robustness and reproducibility of advanced in vitro models.

show abstract

Section: Discussionmentioning

confidence: 95%

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It has been suggested that such a collaboration mechanism could involve NLRP3 inflammasome [ 21 , 65 ] or activation of pro-inflammatory transcription factors [ 65 ]. In the literature, other studies using lung co-culture models reported significant pro-inflammatory effects of SiO 2 [ 21 , 22 ], TiO 2 [ 21 , 43 ], CeO 2 [ 43 ], quartz [ 52 ], PLGA [ 24 ], polystyrene [ 67 ], and CuO [ 65 ] NPs. However, most of these studies either did not compare the inflammatory response measured in co-culture with mono-culture models or compared it only with epithelial cells and not with macrophages [ 43 , 52 , 65 , 67 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the literature, other studies using lung co-culture models reported significant pro-inflammatory effects of SiO 2 [ 21 , 22 ], TiO 2 [ 21 , 43 ], CeO 2 [ 43 ], quartz [ 52 ], PLGA [ 24 ], polystyrene [ 67 ], and CuO [ 65 ] NPs. However, most of these studies either did not compare the inflammatory response measured in co-culture with mono-culture models or compared it only with epithelial cells and not with macrophages [ 43 , 52 , 65 , 67 ]. Among these studies, only Dekali et al have actually demonstrated an increased inflammatory response in co-culture compared to epithelial cells and macrophages in mono-culture as we have [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density

Arezki

Cornacchia

Rapp

et al. 2021

Toxics

View full text Add to dashboard Cite

This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = -43.3 mV); CD-PEI600 (Qek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Qek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Qek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges.

show abstract

“…Basic ALI airway models, consisting of respiratory cells only, are stable for prolonged times. If, however, immune cells are included, particularly when cell lines are used, the model becomes unstable [69]. This is due to the fact that cell types have different requirements for survival and growth.…”

Section: In Vitro Models For the Healthy Lungmentioning

confidence: 99%

Replacement Strategies for Animal Studies in Inhalation Testing

Frőhlich

2021

Sci

Self Cite

View full text Add to dashboard Cite

Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

show abstract

Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure

Cited by 24 publications

References 52 publications

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures

A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density

Replacement Strategies for Animal Studies in Inhalation Testing

Contact Info

Product

Resources

About