Human epidermis reconstructed in vitro: a model to study keratinocyte differentiation and its modulation by retinoic acid.

It was possible to reconstruct epidermis in vitro by seeding dissociated keratinocytes on de-epidermized dermis and growing such recombined cultures for 1 wk, exposed to air, at the surface of the culture medium. These conditions were chosen to mimic the transdermal feeding and the exposure to the atmosphere that occur in vivo. Contrary to classical cultures performed on plastic dishes covered with culture medium, which show rudimentary differentiation and organization, the architecture of the stratified epithelium obtained in reconstructed cultures and the distribution of differentiation markers such as suprabasal keratins, involucrin, and membrane-bound transglutaminase were similar to those of the epidermis of skin biopsies; moreover, biochemical studies showed that the synthesis of the various keratins and the production of cornified envelopes was similar to what is found with skin specimens. The reconstructed epidermis model was found to be very useful to study in vitro the effect of retinoic acid on keratinocyte differentiation and epidermal morphogenesis.