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Review
. 2018 Jun 1;4(2):115-128.
doi: 10.1089/aivt.2018.0002.

Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway

Samantha C Faber  1 , Shaun D McCullough  2
Affiliations
Review

Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway

Samantha C Faber et al. Appl In Vitro Toxicol. .

Abstract

With 7 million deaths reported annually from air pollution alone, it is evident that adverse effects of inhaled toxicant exposures remain a major public health concern in the 21st century. Assessment and characterization of the impacts of air pollutants on human health stems from epidemiological and clinical studies, which have linked both outdoor and indoor air contaminant exposure to adverse pulmonary and cardiovascular health outcomes. Studies in animal models support epidemiological findings and have been critical in identifying systemic effects of environmental chemicals on cognitive abilities, liver disease, and metabolic dysfunction following inhalation exposure. Likewise, traditional monoculture systems have aided in identifying biomarkers of susceptibility to inhaled toxicants and served as a screening platform for safety assessment of pulmonary toxicants. Despite their contributions, in vivo and classic in vitro models have not been able to accurately represent the heterogeneity of the human population and account for interindividual variability in response to inhaled toxicants and susceptibility to the adverse health effects. Development of new technologies that can investigate genetic predisposition, are cost and time efficient, and are ethically sound, will enhance elucidation of mechanisms of inhalation toxicity, and aid in the development of novel pharmaceuticals and/or safety evaluation. This review will describe the classic and novel cell-based inhalation toxicity models and how these emerging technologies can be incorporated into regulatory or nonregulatory testing to address interindividual variability and improve overall human health.

Keywords: in vitro; inhalation; interindividual variability; lung; three-dimensional model; toxicity.

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Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Cell-based in vitro lung models for the study of inhalation toxicity. Visual representation of monoculture and three-dimensional in vitro models and the pros and cons of each model system for the study of inhalation toxicity. (A) Two-dimensional monoculture, (B) organotypic culture, (C) spheroid culture, (D) organoid culture, and (E) microfluidic and microfabricated device culture. ECM, extracellular matrix.
<b>FIG. 2.</b>
FIG. 2.
Generation of specialized patient-specific cells for use in inhalation toxicity testing. Primary airway epithelial cells, hESCs, and iPSCs are generated from a specific donor through distinct culture methods. Each cell type undergoes differentiation to become a specialized patient-specific airway epithelial cell for the use in interindividual screening and inhalation toxicity assessment. hESCs, human embryonic stem cells; iPSCs, induced pluripotent stem cells.
See this image and copyright information in PMC

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