Structural biology of epithelial tissue in histophysiologic gradient culture.

Epithelial cells proliferate, forming organized tissues, when positioned in the lumen of a thin-walled, transparent, elongated cylindrical, cystlike culture chamber. The closed chamber, 2.5 mm in diameter and 25 mm long, bathed in medium, incubated with continuous gentle agitation, enables the inoculum to exchange metabolites including oxygen by diffusion across the thin, nylon filament-reinforced collagen membrane wall of the chamber. After periods of culture of a week or more, using inocula derived from urothelium, the inner surface of the cystic chamber is lined by a stratified epithelium. Proliferation of cells is seen in the basal zone, which is attached to the collagen substrate. The development of the model is briefly described. Some of the applications of the procedure are illustrated using cell lines, chick embryo tissues, and clinical tissues. Implications of the procedure are considered for studying categories of tissue biology, e.g., problems of aging, neoplasia, and toxicology.