Ulti-HEP: A Breakthrough Alternative to Primary and Immortalized Liver Cells

Redefining iPSC-Derived Liver Models for Drug Discovery and Disease Research

Meeting an Urgent Industry Need

 

Drug development is increasingly hindered by a lack of predictive, scalable, and functionally accurate liver models. Traditional in vitro systems such as primary human hepatocytes, suffer from poor longevity, inconsistency, and donor variation leading to low reproducibility. Meanwhile, immortalised cancer cell lines do not offer a phenotypically relevant enough model for efficacy investigations. While iPSC (induced pluripotent stem cell) technology holds promise, conventional iPSC-derived hepatocytes often fall short, displaying immature phenotypes and limited metabolic activity.

DefiniGEN’s next-generation platform directly overcomes these limitations—offering a new standard in hepatocyte functionality and reproducibility.

Lab researcher conducting drug discovery investigations
Opti-HEP_v2

The Ulti-HEP Advantage:

Built upon the pioneering work of Prof Ludovic Vallier, DefiniGEN’s platform represents a significant evolution in iPSC-derived hepatocyte production. Our proprietary 3-step iPSC differentiation protocol has been extensively refined, yielding Ulti-HEP, a best-in-class iPSC-derived hepatocyte with:

  • Enhanced functional maturity

  • Sourced from a single donor

  • Consistent, scalable batch production

  • High-fidelity gene and protein expression profiles

This innovation empowers researchers to make more confident, translationally relevant decisions at the start of their drug discovery and development pipeline.

Learn more about Ulti-HEP

Applications Across the R&D Pipeline

Versatile, Predictive, and Scalable iPSC-Derived Hepatocytes for Every Stage of Development

DefiniGEN’s Ulti-HEP platform is purpose-built to meet the evolving demands of modern drug discovery, toxicology, and disease research. Whether you're exploring disease mechanisms, screening compound libraries, or developing patient-specific models, our wild-type and disease models deliver the physiological relevance and consistency needed to improve translational outcomes and reduce reliance on animal models.

 

Disease Modeling

Accurately replicate human liver diseases using patient-derived iPSCs to explore pathophysiology and therapeutic interventions.

 Drug Safety & Toxicology

Screen compounds for hepatotoxicity and off-target effects using functionally predictive liver cells.

 

Mechanism of Action Studies

Uncover drug targets, validate biological pathways, and understand compound effects at a cellular level.

 

Personalized medicine

Predict individual patient responses through tailored hepatocyte models derived from donor-specific iPSCs.

 

Ulti-HEP is demonstrably superior to conventional iPSC-derived hepatocytes

Through Principal Component Analysis (PCA) we demonstrate that Ulti-HEP clusters closer to Primary human hepatocytes when compared to conventional iPSC-hepatocytes.

Conventional vs. DefiniGEN iPSC-derived hepatocytes

Side 2A - PCA plot v3
Figure 1A: Principal component analysis (PCA) representing the variance in gene expression between conventional and optimised (Ulti-HEP) iPSC-derived hepatocytes across three biological replicates.
Slide 2B - Heat_map_PHH_blue
Figure 1B: Heat map of the expression changes (normalised counts per million) of the top 10 differentially expressed genes (FDR 5%) in conventional and optimised (Ulti-HEP) iPSC-derived hepatocytes and how these compared to primary human hepatocytes (PHH). (FDR corrected P-values <0.05).
Slide 1C - Pathway enrichment KEGG
Figure 1C: Top KEGG pathways illustrated as gene ratio of the differentially expressed genes between conventional and optimised (Ulti-HEP) iPSC-derived hepatocytes contributing to each annotated pathway and coloured with a gradient defined by the statistical significance of pathway enrichment.

Conventional vs. DefiniGEN iPSC-derived hepatocytes: 

Comparing metabolic pathways

mRNA expression levels of the hepatocyte maturity marker albumin
Figure 2A: mRNA expression levels of the hepatocyte maturity marker albumin (ALB) in conventional and optimised iPSC-derived hepatocytes (Ulti-HEP).
mRNA expression levels of the urea cycle genes OTC, ASS1, ASL, ARG1, and CPS1
Figure 2B: mRNA expression levels  of the urea cycle genes OTC, ASS1, ASL, ARG1, and CPS1 in conventional and optimised (Ulti-HEP) iPSC-derived hepatocytes.
mRNA expression levels of the Phase I drug metabolism genes CYP3A4, CYP2B6, CYP2A6, CYP2C9, CYP2C19, and CYP2D6
Figure 2C: mRNA expression levels of the Phase I drug metabolism genes CYP3A4, CYP2B6, CYP2A6, CYP2C9, CYP2C19, and CYP2D6 in conventional and optimised iPSC-derived hepatocytes (Ulti-HEP). Data are presented as mean±SEM of n=2-3 independent experiments.

Frequently asked questions

Contact us

Do Ulti-HEPs express ASGR1?

Yes, ASGR1 and ASGR2 has been detected by qPCR analysis and ICC and has been shown to localize on the cell membrane. 

Do they have a functional urea cycle?

Yes this has been characterized by gene expression profiling, Western blot analysis and Ornithine stimulated functional analysis.

Can you see CYP expression activity?

Expression of CYPs is detectable by qPCR analysis, but they are lower than Primary Human Hepatocytes (PHH).

DefiniGEN-logo

Let’s work together.

Contact us today to speak to one of our experts about how Ulti-HEP can accelerate your research

Resources
Contact Us