Human nasal epithelial cells

Ugwoke MI, Agu RU, Jorissen M, Augustijns P, Sciot R, Verbeke N, Kinget R 2000 Toxicological investigations of the effects carboxymethylcellulose on ciliary beat frequency of human nasal epithelial cells in primary suspension culture and in vivo on rabbit nasal mucosa. Int J Pharm 205 43-51. 

Cultured nasal cells are reliable models for drug transport and metabolism studies, since they are known to express important biological features (e.g. tight junctions, mucin secretion, cilia, and various transporters), resembling those found in vivo systems. Moreover, easy control of experimental conditions as well as separation of the permeation step from the subsequent absorption cascade is also possible. A relatively simple primary culture condition using human nasal epithelial cells for in vitro drug transport studies has been established and applied in transport and metabolism studies of drugs. It is known that the culture condition and/or selection of culture media are critical in the recapitulation of well-differentiation features of in vivo nasal mucosal epithelium [46],... 

RPMI 2650 is the only human nasal epithelial cell line derived from a spontaneously formed tumor. This particular cell line has been mostly used for nasal metabolism studies, since it grows into a multilayer and does not form confluent monolayers (although perijunctional actin rings are present). Thus, RPMI 2650 cell monolayer is rarely used for nasal transport studies [44, 58],... 

Figure 9.1 Relationship between the transepithelial electrical resistance (TEER) value of the passage-cultured human nasal epithelial cell layer and permeability of 14C-mannitol (o, passage-2 A, passage-3 , passage-4) and budesonide ( , passage-2 , passage-3 , passage-4). (Data from Ref. [40]).

Figure 9.2 Relationship between log P values of various drugs and Papp across the passage-cultured human nasal epithelial cell monolayer using LCC method.

For AIC conditions, the apical surface of the epithelial cell layer is exposed to air after the nasal cells reached confluence on the Transwell insert, while the basolateral side is fed with culture fluid. Figure 9.3 shows TEER changes in epithelial cell layers cultured up to 20 days in LCC versus AIC methods [46], In AIC condition (initiated from day 3 after seeding), TEER peaked on day 5 and maintained above the TEER values observed for LCC counterparts. By contrast, TEER observed for LCC conditions peaked on day 2 and declined toward zero by day 15. These data indicate that human nasal epithelial cells at an air interface culture exhibit better electrophysiological characteristics than those cultured by the conventional liquid-covered conditions. 

Figure 9.3 Changes in transepithelial electrical resistance (TEER) of human nasal epithelial cell layers grown under LCC ( ) versus AIC (A) conditions. Each data point represents the mean SD of three determinations. (Data from Ref. [46]).

R. Wu, J. Yankaskas, E. Cheng, M. R. Knowles, and R. Boucher. Growth and differentiation of human nasal epithelial cells in culture. Serum-free, hormone-supplemented medium and proteoglycan synthesis. Am Rev Respir Dis 132 311— 320 (1985). 

C. Mattinger, T. Nyugen, D. Schafer, and K. Hormann. Evaluation of serum-free culture conditions for primary human nasal epithelial cells. Int J Hyg Environ Health 205 235-238 (2002). 

Drug permeability, metabolism, and toxicity can be evaluated in vitro using models of the nasal epithelial in preparation for in vivo experiments. Human nasal epithelial cell cultures and animal nasal mucosa mounted in Ussing chambers provide convenient, simple systems in which drug targeting and absorption mechanisms can be investigated under defined, controlled conditions [45],... 

Agu, R. U., Jorissen, M., Willems, T., Van Den Mooter, G., Kinget, R., and Augustijns, P. (1999), Effects of pharmaceutical compounds on ciliary beating in human nasal epithelial cells A comparative study of cell culture models, Pharm. Res., 16,1380-1385. 

Jorissen, M., Van der Schueren, B., Tyberghein, I, Van Der Berghe, H., and Cassiman, J. J. (1989), Ciliogenesis and coordinated ciliary beating in human nasal epithelial cells cultured in vitro, Acta Oto-Rhino-Laryngol. Begica, 43, 67-73. 

Primary culture of human nasal epithelial cells... 

Sensitization reactions may follow the prolonged application of strong solutions to the skin, although patch tests have shown that chlorocresol is not a primary irritant at concentrations up to 0.2%. Cross sensitization with the related preservative chloroxylenol has also been reported. " "" At concentrations of 0.005% w/v, chlorocresol has been shown to produce a reversible reduction in the ciliary movement of human nasal epithelial cells in vitro and at concentrations of 0.1% chlorocresol produces irreversible ciliostasis therefore it should be used with caution in nasal preparations. " However, a clinical study in asthma patients challenged with chlorocresol or saline concluded that preservative might be used safely in nebulizer solution. ... 

Ayars, G.H., Altman, L.C, Loegering, D.A. and Gleich, G.J. (1991). Eosinophil major basic protein [MBP] up regulates intercellular adhesion molecular-1 [ICAM-1] expression on human nasal epithelial cells [HNE]. J. Allergy Clin. Inununol. 87, 304. 

Kanthakumar, K., Cundell, D.R., Johnson, M., Wills, P.J., Taylor, G.W. and Cole, P.J. (1994). Effect of salmeterol on human nasal epithelial cell ciliary beating inhibition of the ciliotoxin, pyocyanin. Br. J. Pharmacol. 112, 493-498. 

Mallants R, Jorissen M, Augustijns P (2007) Effect of preservatives on ciliary beat frequency in human nasal epithelial cell culture single versus multiple exposure. Int J Pham 338 64—69... 

---