Modular cell culture platform with passive fluid controls for GI tract - Liver tissue co-culture

We have developed a microfluidic cell culture platform and used it to culture GI tract epithelial cells and primary liver cells together for 14 days. In the body, these tissues are responsible for the first pass meatbolism of nutrients and drugs. Both, GI tract epithelium and liver were scaled down from in vivo values by a factor of 110,000. Both tissues were perfused at physiologic fluid flow rates that were controlled via passive device elements. Representing the GI tract epithelium, Caco-2 cells maintained a transepithelial resistance (TEER) of 200 to 380 1/2cm². Representing human liver tissue, a mixture of human primary nonparenchymal cells (fibrolbasts, stellate and Kupffer cells) and parenchymal cells (hepatocytes), maintained urea and albumin synthesis for the entire culture period of 14 days. The modular design enabled us to culture both tissues separate from each other in order to reach maturity before combining them. The device presents a low cost approach to culturing multiple tissue with ratios of tissue volumes and fluid flow rates that are of physiologic relevance.