Models to study molecular, biochemical, and functional responses in vitro generally incorporate an individual cell type or group of cells organized in a random fashion. Normal physiological responses in vivo require that individual cell types be oriented in an organized fashion with three-dimensional architecture and appropriately positioned cellular interfaces. Much recent progress has been made in the development and implementation of models to study Cell-Cell contact using substrate grown cells. Here, we summarize the use of membrane permeable sup-ports to study functional responses in appropriately positioned cell types. These models incorpo-rate two or more different cells cultured in physiologically positioned locales on solid substrates. Models incorporating nonadherent cells (e.g., leukocytes) in co-culture with such models also are discussed. Such models have been used extensively to discovery both cell-bound as well as soluble mediators of physiological and pathophysiological processes.
