Engineering skin to study human disease--tissue models for cancer biology and wound repair.

Recent advances in the engineering of three-dimensional tissues known as skin equivalents, that have morphologic and phenotypic properties of human skin, have provided new ways to study human disease processes. This chapter will supply an overview of two such applications--investigations of the incipient development of squamous cell cancer, and studies that have characterized the response of human epithelium during wound repair. Using these novel tools to study cancer biology, it has been shown that cell-cell interactions inherent in three-dimensional tissue architecture can suppress early cancer progression by inducing a state of intraepithelial dormancy. This dormant state can be overcome and cancer progression enabled by altering tissue organization in response to tumor promoters or UV irradiation or by modifying the interaction of tumor cells with extracellular matrix proteins or their adjacent epithelia. By adapting skin equivalent models of human skin to study wound reepithelialization, it has been shown that several key responses, including cell proliferation, migration, differentiation, growth-factor responsiveness and protease expression, will mimic the response seen in human skin. In this light, these engineered models of human skin provide powerful new tools for studying disease processes in these tissues as they occur in humans.