ATLA::Alternatives to Laboratory Animals

Volume 23, Number 1

Reconstructed human epidermis in vitro: an alternative to animal testing.

ATLA 23, 97-110, January/February 1995

Maria Ponec

Department of Dermatology, University Hospital Leiden, P.O. Box 9600, 2300 RC Leiden, The Netherlands

SUMMARY

Various three-dimensional human skin models, in which the epidermis exhibits in vivo-like morphological and functional characteristics, have recently been developed. Such models are currently being used to study the development and physiology of the skin, the processes involved in wound healing, and the reactivity of skin to environmental and chemical insults. Since these models reproduce to a large extent the barrier function properties of normal human skin, they can be used for screening potential skin irritants. These substances can be applied topically and their irritant potential can be evaluated using various endpoints, such as the induction of tissue damage or the release of various pro-inflammatory mediators. Studies with human skin equivalents can therefore contribute to our knowledge of the basic biochemical mechanisms underlying irritant reactions, and can be used to understand the structural features of molecules which may be responsible for eliciting an irritant reaction. In addition, the generation of epidermal equivalents populated with melanocytes, as well as keratinocytes, makes it possible to study the regulation of melanogenesis, melanocyte keratinocyte interactions, and how these are affected by W irradiation. Such a model can also be used for testing the phototoxic or photoprotective potentials of various compounds and sunscreens.

Keywords: human skin models, reconstructed human epidermis, epidermal differentiation, in vitro toxicological tests, interleukins, integrins, skin barrier function, keratinocyte-melanocyte co-culture