Organovo Webinar Series 4

Modeling NAFLD and TGFβ-induced Fibrosis in ExVive™ Human Liver Tissue

Presented live on June 8, 2017

Panelists: Jeff Irelan, Ph.D., Director, Scientific Applications, Organovo
and Alice Chen, Ph.D., Associate Director, Tissue Applications, Organovo
Moderator: Tom Murphy, Ph.D., Director, Scientific Applications, Organovo

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder with an estimated prevalence of over 25% worldwide and is projected to become the leading indication for liver transplant by 2025. Despite decades of research focused on NAFLD, an effective treatment has yet to be approved. This is due in part to the reliance on cell culture and animal models that present challenges in translation due to limited functional longevity and species differences, respectively.

ExVive™ Human Liver Tissue, a clinically-translatable in vitro model, is ideal for studying the effects of drugs on liver disease progression, regression, and the mechanisms involved. Here we present results showing a nutrient overload induction of liver disease and TGFβ-induced fibrosis in ExVive™ Human Liver Tissue. A variety of disease-relevant phenotypes including steatosis, inflammation, and fibrosis can be demonstrated in the model:

  • Nutrient overload leads to the accumulation of lipid droplets in hepatocytes.
  • Incorporation of Kupffer cells and stimulation with inflammatory signals induces inflammatory cytokine release.
  • Chronic exposure to inflammatory inducers and nutrient overload leads to stellate cell activation and fibrosis.
  • Chronic exposure to chemical inducers of fibrosis or TGFβ stimulation leads to stellate cell activation and fibrosis.
  • A TGFβR1 kinase inhibitor effectively blocks TGFβ-induced fibrosis.