We will develop a commercial kit so that biologists can readily study tissues under conditions of histophysiologic gradient culture. Here, as in nature, stratified epithelia adhere to their supporting stroma at a recognizable interface. Renewal of epithelium occurs adjacent to the interface, and all metabolic exchange is by diffusion across the interface. In culture, a thin, transparent, permeable collagen membrane serves as a "stroma." Cells attach to one surface of the membrane, the medium bathes the opposite side, and metabolic exchange for the cells is by diffusion across the collagen. The side of the membrane in contract with the cells is waffled with collagen, which increases the tensile strength of the membrane and the surface area for cell attachment. The membrane is used in two configurations, as a flat substrate, and as a thin cylindrical chamber closed at both ends. With commercial kits available, a number of basic and clinical biomedical applications will follow. Processes of tissue remodeling, aging, metaplasia,atrophy, hypertrophy, dysplasia, carcinogenesis, intra-epithelial invasion, and viral propagation can be reconstituted and manipulated. Clinical applications are numerous too, both in diagnosis and treatment,e.g. characterization of cells from a biopsy that will predict the subsequent course.National Cancer Institute (NCI)
