Improved in vitro and in vivo concordance in gene expression using co-culture models
Researchers from West Virginia University and the National Institute for Occupational Safety and health (NIOSH), who elucidated toxicity pathways involved in mouse pulmonary exposures to multi-walled carbon nanotubes in previous publications, have now begun to investigate the use of in vitro cellular models for assessing nanoparticle toxicity.
In a recent publication in the journal Toxicology, Snyder-Talkington, et al. (2015) found that a more complex co-culture model provided toxicity testing results better aligned with those from in vivo studies. “This study compared global multi-walled carbon nanotube (MWCNT)-induced gene expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with gene expression from mouse lungs exposed to MWCNT….[and] determined that there were more concordant genes (gene expression both up- or downregulated in vivo and in vitro) expressed in both cell types in coculture than in monoculture.”
“Additionally, different cellular signaling pathways are activated in response to MWCNT dependent upon culturing conditions.” Some of the specific pathways linked to the in vivo/in vitro concordant genes are identified in the paper, and include pathways related to lung inflammation and fibrosis.
Assay endpoint differences and improved performance have sometimes been reported when co-culture and/or 3D cell-based models are used for chemical toxicity testing. However, the data for making direct in vivo/in vitro pathway-level comparisons is usually not available. Snyder-Talkington, et al. indicate that their studies may be the first transcriptomic comparisons of cell-based models with in vivo gene expression. They appear to be on the right track toward developing a cell-based model useful in predicting human inhalation toxicity to carbon nanotubes.
Citation to the article discussed here:
Snyder-Talkington, B.N., Dong, C., Zhao, X., Dymacek, J., Porter, D.W., Wolfarth, M.G., Castranova, V., Qian, Y. & Guo N.L. (2015). Multi-walled carbon nanotube-induced gene expression in vitro: Concordance with in vivo studies. Toxicology 328, pp. 66–74.
Posted: February 4, 2015