Publication Summary:

Translation of preclinical data to clinical outcomes remains an ongoing challenge in drug development. 3D bioprinted tissues exhibiting physiological tissue-like responses can be created to bridge this gap, through spatially controlled, automated deposition of tissue-specific cell types. These multicellular, human in vitro tissue models enable improved cellular interactions and assessment of biological responses at the biochemical, genomic, and histological levels over extended time in culture. Organovo’s ExVive™ Human Liver can be used to model chronic liver disease relevant phenotypes including steatosis, inflammation, and fibrosis. Incorporation of Kupffer cells and stimulation with inflammatory signals induces inflammatory cytokine release. Chronic exposure to drugs known to induce steatosis such as valproic acid, or to nutrient overload (free fatty acids) induces formation of lipid droplets. Chronic exposure to chemical inducers of fibrosis or TGFβ stimulation leads to stellate cell activation and fibrosis. Finally, inflammatory inducers and nutrient overload together lead to steatosis and fibrosis. These results suggest that ExVive™ Human Liver Tissue holds promise for the study of complex, chronic conditions such as NASH, enabling the discovery of novel therapeutics, biomarkers and safety assessment of drugs in a disease-relevant background.