This Frontiers review analyzes the rapidly growing microfluidic strategies that have been employed in attempts to create physio relevant 'organ-on-chip' models using primary tissue removed from a body (human or animal). Tissue harvested immediately from an organism, and cultured under artificial conditions is referred to as ex vivo tissue. The use of primary (organotypic) tissue offers unique benefits over traditional cell culture experiments, and microfluidic technology can be used to further exploit these advantages. Defining the utility of particular models, determining necessary constituents for acceptable modeling of in vivo physiology, and describing the role of microfluidic systems in tissue modeling processes is paramount to the future of organotypic models ex vivo. Virtually all tissues within the body are characterized by a large diversity of cellular composition, morphology, and blood supply (e.g., nutrient needs including oxygen). Microfluidic technology can provide a means to help maintain tissue in more physiologically relevant environments, for tissue relevant time-frames (e.g., matching the natural rates of cell turnover), and at in vivo oxygen tensions that can be controlled within modern microfluidic culture systems. Models for ex vivo tissues continue to emerge and grow in efficacy as mimics of in vivo physiology. This review addresses developments in microfluidic devices for the study of tissues ex vivo that can serve as an important bridge to translational value.

A microfluidic organotypic device that maintains mouse colon explants for up to 72 h in a physiologically relevant environment is reported. The device is easy to assemble and maintains physiologically accurate oxygen concentrations across the tissue.

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods (synapse.org/LINCS_MCF10A). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.