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

Datum

23.06.2017

Zeit

10:00 - 11:00

Sprecher

Christine Daly

Zugehörigkeit

Organovo Inc., UK

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie

Host

Marc Bickle

Beschreibung

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 induces inflammatory cytokine release. - Chronic exposure to 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.

Letztmalig verändert: 24.06.2017, 09:46:23