Human Tissue in the Evaluation of Safety and Efficacy of New Medicines: A Viable Alternative to Animal Models?
Some examples of tests involving cell cocultures. Such methods allow simultaneous application of compounds to multiple cell types, means of studying the influence (e.g., via secreted factors) of one cell type over the other, and of the effects of metabolites produced by one cell type on the function of another. (a) IdMOC technology. Typically, cells are seeded in inner wells (marked in green) and incubated for 24 hours to allow attachment, after which the larger, rectangular (yellow), well is flooded with media containing substrates or test compounds. The flooding medium permits interconnection of multiple inner wells cell mimicking the integration of multiple organs via the systemic circulation. (b) Upper panel shows quasivivo system, lower panel a schematic showing how chambers can be connected in series with different cell types in each. The first chamber A1 is a dual flow chamber with different liquids/media on either side of a porous membrane or scaffold on which cells are being cultured. The A1 type of chamber can be adapted to provide an air-liquid interface by substituting one of the liquid flows by air. (c) Lung on a chip. Upper panel shows the chips, lower panel a schematic illustrating the detail of the design and the arrangement of bronchial epithelial and airway vascular endothelium either side of a porous membrane. Chips are 2 cm—long polymer devices designed to mimic the function of the human lung. The microfluidics system incorporates an alveolar-capillary interface that is flanked by two side chambers. The alveolar-capillary interface consists of a porous, flexible, 10 μm—thick polymer membrane coated with extracellular matrix (ECM) that separates a channel containing human alveolar epithelial cells and a layer of air from a channel containing human pulmonary microvascular endothelial cells and a flowing layer of cell culture media. Application of vacuum to the side chambers deforms the thin walls separating those chambers from the interface, causing the flexible polymer membrane to stretch—thus mimicking the mechanical effects of breathing.
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