(J-378) A Multiwell Platform to Elucidate the Species-Specific Effects of Oxygen Tensions on Primary Hepatocytes

Hepatocyte functions are differentially expressed along the length of the liver sinusoid in response to gradients of oxygen (~10% to 3%) and other soluble factors such as hormones and nutrients. These zonated functions include glucose production, activities of drug metabolism enzymes, and nitrogen metabolism. Liver zonation has been implicated in the toxicity of several drugs and the initiation of metabolic fatty liver disease in the low-oxygen regions of the liver. While there have been some attempts at leveraging microfluidic platforms to induce zonation in primary hepatocytes, such devices cannot fully decouple the effects of different soluble factor gradients to precisely elucidate the effects on cell phenotypes. Furthermore, primary hepatocytes lose phenotype functions in conventional monocultures, even within microfluidic devices, which does not allow a physiological representation of their zonated responses. Thus, here we engineered micropatterned co-cultures (MPCCs) of primary hepatocytes and supportive fibroblasts onto custom-built gas-permeable multi-well plates towards elucidating the effects of precise oxygen tensions on the long-term and species-specific zonated functions of both rat and human hepatocytes.