Peer-Reviewed Publications

      Impact assessment of cigarette smoke exposure on organotypic bronchial epithelial tissue cultures: A comparison of mono-culture and coculture model containing fibroblasts

      Iskandar, A. R.; Xiang, Y.; Frentzel, S.; Talikka, M.; Leroy, P.; Kuehn, D.; Guedj, E.; Martin, F.; Mathis, C.; Ivanov, N. V.; Peitsch, M. C.; Hoeng, J.
      Published
      Jun 16, 2015
      DOI
      10.1093/toxsci/kfv122
      PMID
      26085348
      Link to publication
      Topic
      Summary

      Organotypic 3D cultures of epithelial cells are grown at the air-liquid interface (ALI) and resemble the in vivo counterparts. Although the complexity of in vivo cellular responses could be better manifested in co-culture models in which additional cell-types such as fibroblasts were incorporated, the presence of another cell-type could mask the response of the other. This study reports the impact of whole cigarette smoke (CS) exposure on organotypic mono- and co-culture models to evaluate the relevancy of organotypic models for toxicological assessment of aerosols. Two organotypic bronchial models were directly exposed to low and high concentrations of CS of the reference research cigarette 3R4F: mono-culture of bronchial epithelial cells without fibroblasts (BR) and co-culture with fibroblasts (BRF) models. Adenylate kinase-based cytotoxicity, cytochrome P450 (CYP) 1A1/1B1 activity, tissue histology, and concentrations of secreted mediators into the basolateral media, as well as transcriptomes were evaluated following the CS exposure. The results demonstrated similar impact of CS on the AK-based cytotoxicity, CYP1A1/1B1 activity, and tissue histology in both models. However, a greater number of secreted mediators was identified in the basolateral media of the mono-culture than in the co-culture models. Furthermore, annotation analysis and network-based systems biology analysis of the transcriptomic profiles indicated a more prominent cellular stress and tissue damage following CS in the mono-culture epithelium model without fibroblasts. Finally, our results indicated that an in vivo smoking-induced xenobiotic metabolism response of bronchial epithelial cells was better reflected from the in vitro CS-exposed co-culture model.

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.