NAFLD & NASH MODELLING

Non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver disorder worldwide, affecting approximately 25% of the global population. NAFLD is characterised by a spectrum of liver pathologies varying from hepatic steatosis to non-alcoholic steatohepatitis (NASH), which can evolve towards fibrosis, cirrhosis and hepatocellular carcinoma. The global incidence of NAFLD and NASH is steadily rising, however development of pharmacological interventions remains hampered by the lack of human relevant and sensitive models for disease modelling and screening purposes.

Insulin driven de novo lipogenesis screening

IVTD’s patented human skin stem cell-derived hepatic cell model (hSKP-HPC or HepaSTARs) is a sensitive high throughput model that reflects non-alcoholic fatty liver disease (NAFLD) pathogenesis, applicable for the identification of novel drug candidates that impact hepatic insulin-driven de novo lipogenesis (DNL). The model has been validated through ongoing industry partnerships and outperforms human hepatocytes, HepG2 and iPSC-hepatocytes for insulin driven hepatic DNL responsiveness.

PUBLICATIONS

Human hepatocyte-like cells as relevant in vitro model for hepatic insulin-driven de novo lipogenesis (2020, in preparation)

In vitro NASH

The induced NASH hSKP-HPC model can exhibit different NAFLD severities and key features of human NASH pathology. The model reflects the mechanisms involved in the development of the disease, is responsive to known anti-NASH compounds, including elafibranor and can be used to screen and select novel drug candidates for the treatment of NASH.

Publications

Current projects

led by Tamara Vanhaecke and Robim Rodrigues

LIPOSTEM: In vitro model based on human skin-derived stem cells to study de novo lipogenesis toward high throughput target identification and screening
Investigating the impact of PNPLA3 genetic polymorphism on the development and treatment of non-alcoholic steatohepatitis (NASH): an in vitro study using human stem cell-derived hepatic cells.

Seeking collaborations/candidates

led by Tamara Vanhaecke

• miniaturisation of induced hSKP-HPC NASH model towards high-throughput drug screening