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dc.contributor.authorSusewind, Julia
dc.contributor.authorde Souza Carvalho-Wodarz, Cristiane
dc.contributor.authorRepnik, Urska
dc.contributor.authorCollnot, Eva-Maria
dc.contributor.authorSchneider-Daum, Nicole
dc.contributor.authorGriffiths, Gareth Wyn
dc.contributor.authorLehr, Claus-Michael
dc.date.accessioned2017-03-29T12:57:20Z
dc.date.available2017-03-29T12:57:20Z
dc.date.issued2016
dc.identifier.citationA 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials. 2016, 10 (1):53-62 Nanotoxicologyen
dc.identifier.issn1743-5404
dc.identifier.pmid25738417
dc.identifier.doi10.3109/17435390.2015.1008065
dc.identifier.urihttp://hdl.handle.net/10033/620876
dc.description.abstractOral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation.
dc.language.isoenen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/ 228625en
dc.rightsopenAccessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshCaco-2 Cellsen
dc.subject.meshCoculture Techniquesen
dc.subject.meshHumansen
dc.subject.meshInflammationen
dc.subject.meshInterleukin-8en
dc.subject.meshIntestinal Mucosaen
dc.subject.meshMetal Nanoparticlesen
dc.subject.meshNanostructuresen
dc.subject.meshTitaniumen
dc.titleA 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Institut für Pharmaceutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalNanotoxicologyen
refterms.dateFOA2018-06-12T17:34:53Z
html.description.abstractOral exposure to nanomaterials is a current concern, asking for innovative biological test systems to assess their safety, especially also in conditions of inflammatory disorders. Aim of this study was to develop a 3D intestinal model, consisting of Caco-2 cells and two human immune cell lines, suitable to assess nanomaterial toxicity, in either healthy or diseased conditions. Human macrophages (THP-1) and human dendritic cells (MUTZ-3) were embedded in a collagen scaffold and seeded on the apical side of transwell inserts. Caco-2 cells were seeded on top of this layer, forming a 3D model of the intestinal mucosa. Toxicity of engineered nanoparticles (NM101 TiO2, NM300 Ag, Au) was evaluated in non-inflamed and inflamed co-cultures, and also compared to non-inflamed Caco-2 monocultures. Inflammation was elicited by IL-1β, and interactions with engineered NPs were addressed by different endpoints. The 3D co-culture showed well preserved ultrastructure and significant barrier properties. Ag NPs were found to be more toxic than TiO2 or Au NPs. But once inflamed with IL-1β, the co-cultures released higher amounts of IL-8 compared to Caco-2 monocultures. However, the cytotoxicity of Ag NPs was higher in Caco-2 monocultures than in 3D co-cultures. The naturally higher IL-8 production in the co-cultures was enhanced even further by the Ag NPs. This study shows that it is possible to mimic inflamed conditions in a 3D co-culture model of the intestinal mucosa. The fact that it is based on three easily available human cell lines makes this model valuable to study the safety of nanomaterials in the context of inflammation.


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