Comparison of the basic morphology and function of 3D lung epithelial cultures derived from several donors

• Published in: Current research in toxicology Vol. 1; pp. 56 - 69
• Main Authors: Bovard, David, Giralt, Albert, Trivedi, Keyur, Neau, Laurent, Kanellos, Petros, Iskandar, Anita, Kondylis, Athanasios, Luettich, Karsta, Frentzel, Stefan, Hoeng, Julia, Peitsch, Manuel C.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.06.2020; Elsevier
• Subjects: Bronchial culture; Donor variability; Lung toxicology; Organotypic; Small airway culture; PBS; Lung toxicology; CBF; TCDD; Bronchial culture; Small airway culture; Donor variability; MUC5AC; Organotypic; TEER; CYP; BTUB4; ALI
• ISSN: 2666-027X; 2666-027X
• DOI: 10.1016/j.crtox.2020.08.002

In vitro models of the human lung play an essential role in evaluating the toxicity of inhaled compounds and understanding the development of respiratory diseases. Three-dimensional (3D) organotypic models derived from lung basal epithelial cells and grown at the air–liquid interface resemble human airway epithelium in multiple aspects, including morphology, cell composition, transcriptional profile, and xenobiotic metabolism. Whether the different characteristics of basal cell donors have an impact on model characteristics and responses remains unknown. In addition, studies are often conducted with 3D cultures from one donor, assuming a representative response on the population level. Whether this assumption is correct requires further investigation. In this study, we compared the morphology and functionality of 3D organotypic bronchial and small airway cultures from different donors at different weeks after air-lift to assess the interdonor variability in these parameters. The thickness, cell type composition, and transepithelial electrical resistance varied among the donors and over time after air-lift. Cilia beating frequency increased in response to isoproterenol treatment in both culture types, independent of the donor. The cultures presented low basal cytochrome P450 (CYP) 1A1/1B1 activity, but 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment induced CYP1A1/1B1 activity regardless of the donor. In conclusion, lung epithelial cultures prepared from different donors present diverse morphology but similar functionality and metabolic activity, with certain variability in their response to stimulation. [Display omitted] •3D lung cultures derived from various donors differed mostly at the morphological level.•Epithelial thickness, presence of cysts, ciliation, and goblet cell number are donor dependent.•Cilia beating frequency varied across donors but the response to isoproterenol was similar.•CYP450 activity in response to xenobiotics was preserved across donors.