iPSC-derived MASLD model

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) 

MASLD is a spectrum of disease ranging from lipid accumulation within hepatocytes to steatohepatitis with inflammation (MASH), fibrosis, cirrhosis, and can eventually lead to the development of hepatocellular carcinoma.

Using our proprietary Ulti-HEP platform, we have developed a novel in vitro MASLD model that recapitulates the disease phenotype in-a-dish, offering an optimized model for drug discovery applications and a principal tool for elucidating the underlying mechanisms of the disease.

Limitations in animal and primary cell models

Current animal and primary hepatocyte models used to study MASH and MASLD, are widely used because they replicate certain aspects of human metabolic processes. These models often use high-fat diets or genetic modifications to induce MASLD. 

Do not recapitulate human metabolism

Other models do not fully mimic the complexity of human metabolism or the multifactorial nature of the condition. This gap limits the translation of findings to human clinical outcomes​ leading to unsuitable compounds being selected for during screening investigations.

Unsuitable for high throughput screening

Primary hepatocyte models, offer more human-relevant insights, particularly when used in co-cultures. While they are useful for studying inflammation, fibrosis, and lipid metabolism, these cells have limitations such as short lifespan, loss of functionality in culture, and donor variability, which can affect reproducibility and scalability. 

Our Ulti-HEP cells accurately recapitulates the MASLD phenotype when they are treated with high-sugar or high-fat diets, whilst also being scalable and sourced from a single donor, thereby generating reproducible data.

Our Ulti-HEP model de-risks drug discovery by providing a new and highly predictive in vitro screening platform suitable for high throughput studies.

MASLD-associated gene variants

In the last 20 years, genome-wide association studies (GWAS) have identified common single-nucleotide polymorphisms in a variety of genes as main determinants of MASLD.  

Of those, the most common disease-implicated genetic variant is I148M in the gene coding for Patatin-like phospholipase domain-containing protein 3 (PNPLA3). Using CRISPR/Cas9 technology, we have generated gene-edited Ulti-HEP models carrying the I148M mutation and demonstrated the detrimental effects of genetic variation on MASLD development.

This cell line is ideally suited for researchers who are specifically interested in modelling or screening compounds against hepatocytes with the PNPLA3 mutation. As with our wildtype Ulti-HEP cells, this mutated cell line is human-derived and source from a single donor, allowing you to scale your research as necessary whilst maintaining no batch-to-batch variation between cells.