Monoculture cell lines
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Easy to grow and maintain
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Inexpensive
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Amenable to high-throughput screening
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Reproducible toxicity responses
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High viability in comparison to other models
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Available for different cell types present in the respiratory tract
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Availability/standardization allows for comparison of results among different groups
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From one donor, which does not account for population response variability
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In cancer/transformed cell lines, genetic and epigenetic profiles differ from non-cancer cells
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Depending on cell line, limited representation of an in vivo epithelial barrier
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Findings are limited to one cell type
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Cells from human donors
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Allows for evaluation of specific subpopulation of interest (e.g., age, disease, sex, etc.)
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Allows for identification of cell populations with increased susceptibility to adverse effects
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Improved physiological relevance
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Evaluation of responses across multiple cell types
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Can be maintained in culture for weeks/months at a time
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Can be used for repeated exposures to simulate chronic conditions
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Expensive
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Requires more advanced cell culture capabilities
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Time and resource intensive to process and maintain cell culture
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Difficult to determine which cell type drives observed toxicity
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Lung-on-a-chip
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Improved physiological relevance due to potential cell-to-cell communications
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Continuous replenishment of nutrients and removal of waste
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Can model influence of circulating immune cells
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Includes physical and mechanical properties involved in in vivo pulmonary functions
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Can allow for organ-crosstalk (e.g., body-on-a-chip)
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Difficulties surrounding ease of use
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Expensive
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More chronic exposures are currently difficult due to viability considerations
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Technologies are more recently developed and may require further testing
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Insufficient biological material for downstream analyses
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