In vitro reconstituted skin as a tool for biology, pharmacology and therapy: a review

Various culture procedures, suitable to maintain the differentiated phenotype of various types of cells in vitro, have been devised during the past decade. These culture systems use macromolecular components extracted from extracellular matrixes or synthetic polymers which provide cells with a three-dimensional, spatially structured support. Substantial information has come from the use of collagen lattices. Many types of cells, of mesenchymal or other origin, are able to organize collagen fibrils in these models and to form a connective tissue-like structure. Prerequisites for this process are active function of the cytoskeleton and the expression of alpha(2)beta(1) integrin collagen receptors. Interaction of cells with such a matrix has profound effects on morphologic status, proliferation, cellular metabolism, and state of differentiation. The in vitro procedures reviewed and described in this article offer the possibility to combine different types of cells to approximate the in vivo environment and to investigate such physiologic processes as cell-cell and cell-matrix interactions which are otherwise not easily accessible. In pathologic conditions of the skin, these models have proven to be useful tools in investigating diseases relating to impaired recognition of extracellular matrix structures or alterations of cytoskeletal assembly. In pharmacologic and toxicologic studies, activity of drugs and potentially useful therapeutic substances has been evaluated. The use of cells and matrix components derived from skin has lead to refined systems which could be adapted and extended to other organs in an attempt to better understand pathophysiologic mechanisms.