The use of in vitro reconstituted human skin in dermotoxicity testing.

As they simulate the multilayer tissue architecture present in vivo, three-dimensional (3D) cultures of skin epithelial cells represent an attractive alternative for in vitro irritancy testing. In this study histology of non-commercial (Skin recombinant on de-epidermized dermis) and commercial models (Episkin, ZK 1300, Living Skin Equivalent) was compared. All 3D models possess a stratified epidermis with a differentiated stratum corneum. Their barrier function has been demonstrated by comparison of surfactants cytotoxicity on the 3D models and on human keratinocyte monolayer culture, and by the evaluation of the tritiated water penetration. All the 3D models showed permeability higher than fresh skin, the skin recombinant on DDED being the less permeable. However, reconstituted skin models possess several advantages for dermotoxicity testing, including the standardized nature of the epithelia and their suitability for testing water-insoluble compounds.

[1]  J. Brussee,et al.  Toxicity screening of N-alkylazacycloheptan-2-one derivatives in cultured human skin cells: structure-toxicity relationships. , 1989, Journal of pharmaceutical sciences.

[2]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[3]  J. Schweizer,et al.  Expression of high molecular weight (67K) keratin in human keratinocytes cultured on dead de-epidermized dermis. , 1986, Experimental cell research.

[4]  U. Reichert,et al.  Antirespiratory and antiproliferative activity of anthralin in cultured human keratinocytes. , 1985, The Journal of investigative dermatology.

[5]  D. Woodley,et al.  Methods for cultivation of keratinocytes with an air-liquid interface. , 1983, The Journal of investigative dermatology.

[6]  N. Parenteau,et al.  The living skin equivalent: Its manufacture, its organotypic properties and its responses to irritants. , 1991, Toxicology in vitro : an international journal published in association with BIBRA.

[7]  C. Willis,et al.  Epidermal damage induced by irritants in man: a light and electron microscopic study. , 1989, The Journal of investigative dermatology.

[8]  J. Thivolet,et al.  In vitro and post-transplantation differentiation of human keratinocytes grown on the human type IV collagen film of a bilayered dermal substitute. , 1991, Experimental cell research.

[9]  John H. Draize,et al.  METHODS FOR THE STUDY OF IRRITATION AND TOXICITY OF SUBSTANCES APPLIED TOPICALLY TO THE SKIN AND MUCOUS MEMBRANES , 1944 .