TABLE 6

Extrapolating results from models to applications in the human disease: in vivo and in vitro variables and implications

ConsiderationVariablesImplicationsReferences
In vivo
 Animal species/strainRodent, large animalComparative biology of animal versus human lungs[S42, S43]
Genetic factorsStrain variation in phenotypic responses[S44]
ControlsWildtype versus littermates[S45]
 Animal age/sexYoung versus oldDisease prevalence in various age groups[S46]
Male versus femaleDisease prevalence in certain sex[S46]
 Housing conditionsSpecific pathogen free, gnotobiotic, germ-freeMicrobiome influences on phenotypic responses[S47–S49]
 Day/night cyclesCircadian variations in phenotype[S50]
 Variations in temperature of the housing[S51]
 Anesthesia/euthanasiaCellular behaviour and phenotypic responses affected by drugs[S52–S56]
 Staff handling the animals (stress)[S51]
Type of exposures (intranasal/intratracheal instillation, aerosol, etc.)[S57]
In vitro
 Cell typeAuthentication of cell typeSkewing of conclusions if cell type tested is not correct[S58, S59]
 Culture conditionsMediaMedia additives may affect cell behaviour[S58]
MatricesMatrices may affect cell phenotype[S60–S64]
Dimensionality/mechanicsCells behave differently in two versus three dimensions, and on varying stiffnesses[S65–S68]

For references listed in the table please refer to the supplementary material.