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Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non‐Animal Methods for Hazard Assessment
Author(s) -
Ndika Joseph,
Ilves Marit,
Kooter Ingeborg M.,
GröllersMulderij Mariska,
Duistermaat Evert,
Tromp Peter C.,
Kuper Frieke,
Kinaret Pia,
Greco Dario,
Karisola Piia,
Alenius Harri
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202000527
Subject(s) - in vivo , in vitro , transcriptome , microbiology and biotechnology , biology , innate immune system , immune system , nanotoxicology , computational biology , immunology , animal model , lung , gene , chemistry , medicine , toxicity , genetics , gene expression , organic chemistry , endocrinology
The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non‐animal approaches to health hazard assessment for ethical and practical reasons. Although non‐animal approaches are becoming increasingly popular, there are almost no studies of side‐by‐side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air–liquid interface (ALI) cultures of donor‐derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.