Cell Based Products

iPSC-derived Human Hepatocytes: Glycogen Storage Disease Type 1 Alpha

DefiniGEN provides iPSC-derived Glycogen Storage Disease Type 1 Alpha (GSD1A) hepatocytes that are suitable to study disorders related to glycogen storage. This genetic disease results from a deficiency in the glucose-6 phosphatase (G6P) enzyme which impairs the ability of the liver to produce free glucose from glycogen.

These cells can offer disease modeling and drug discovery researchers a tool to develop new therapies for this and similar lysosomal storage diseases or to further the understanding of the disease mechanisms.

We offer two patient lines with different genotypes: homozygous R83C in G6PC and compound heterozygous with G222R and Q347X mutations in G6PC.

Hydrogel-based encapsulated cells

Hydrogel-based encapsulation of Opti-HEP and disease models

We can also transport Opti-HEP and disease models by encapsulating them in Aterlerix’s hydrogel in 96-well plates under normoxic conditions
This allows for the transport of plates over long distance for large-scale screening, efficacy and predictive toxicology studies
This live plate format removes the variation introduced by the cryopreservation and thawing process
Hydrogel-based encapsulation of cells shows comparable cell viability to non-encapsulated cells and comparable expression of hepatocyte maturity markers (ALB, A1AT and HNF4A)

Opti-HSC:

iPSC-derived Human Hepatic Stellates

Introducing the first commercially available iPSC-derived human hepatic stellates, our Opti-HSC are ready for large-scale screening of antifibrotic drugs and in vitro disease modelling.

Unlike primary cells, our hepatic stellate cells are derived from a single donor, ensuring no donor-to-donor variation and providing researchers with reproducible results. Our cells are scalable, unlike primary cells, so that we can meet your needs and facilitate more efficient and effective drug discovery whilst reducing the need for animal models.

Wild-Type:

iPSC-derived Human Intestinal Organoids

DefiniGEN's iPSC-derived Wild-Type Intestinal Organoids provide a unique in vitro system to model the human intestine.

The organoids display a polarized epithelium and harbor a mixture of cell types normally present in the primary intestinal epithelial barrier in vivo, including goblet cells, Paneth cells, enterocytes and enteroendocrine cells. The cells can be used for drug absorption, metabolism and the modeling of infectious disease.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) model

When our Opti-HEP (Wild-Type hepatocytes) are treated with high glucose or high fat diets, they demonstrate increased lipid accumulation, insulin resistance, lipotoxicity and inflammation. This makes them an accurate and ideal human-derived model to screen compounds in high-throughput investigations.

We also offer iPSC-derived MASLD hepatocytes that have been edited to include some of the most common genetic variants implicated in the disease. One of the lines includes the missense homozygous mutation I148M in the gene coding for Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and another line harbors the homozgyous E167K mutation in the gene encoding for Transmembrane 6 Superfamily Member 2 (TM6SF2).

Alpha-1 Antitrypsin Deficiency model

Our iPSC-derived Alpha-1 Antitrypsin Deficiency (A1ATD) hepatocytes are highly functional and showcase a strong diseased phenotype in vitro.

Cells are derived from either A1ATD patients or generated through CRISPR engineering and carry the 'Z' (E342K) point mutation in the SERPINA1 gene. This mutation leads to the accumulation of polymeric aggregates of the proteins that ultimately cause liver and lung damage. Our A1ATD hepatocytes represent an optimized disease model for drug discovery applications and are an effective tool for elucidating the underlying mechanisms of the disease.

We also offer homozygous patient-derived A1ATD cells and both homozygous and heterozygous CRISPR-engineered A1ATD lines.

Wilson's Disease model

DefiniGEN's iPSC-derived Wilson's Disease (WD) hepatocytes provide a highly characterized disease modeling platform to study this rare disease.

Cells are generated through CRISPR engineering and carry the homozygous H1069Q mutation in the ATP7B gene. This mutation causes a decrease in the protein function and leads to excessive accumulation of copper that can cause damage to the liver, brain and other vital organs. Our iPSC-derived WD hepatocytes are a powerful tool for drug discovery applications and can help investigate this monogenic disease and other conditions related to oxidative stress.

Urea Cycle Disorder models

Using our Wild-Type Opti-HEP and CRISPR technology, we have created two different disease models: Ornithine Transcarbamylase Deficiency (OTCD) and Citrullinemia.

Our OTCD disease model carries the D175V mutation (GAT>GTT) on the OTC gene and decreased OTC protein expression and urea secretion compared to Wild-Type Opti-HEP. The Citrullinemia disease model carries the G390R mutation (GGG>AGG) in the ASS1 gene. This model demonstrates decreased ASS1 protein expression compared to Wild-Type Opti-HEP.

Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2) disease model

Our novel, iPSC-derived PFIC2 model, is created using CRISPR-Cas9 technology and is the first of its kind to accurately replicate the PFIC2 phenotype in vitro.

This iPSC-derived model exhibits relevant biological characteristics, ensuring reproducible data without any batch-to-batch variation, making them an ideal tool for drug screening and gene delivery system testing. DefiniGEN’s PFIC2 model allows for large-scale and phenotypically accurate screening of potential treatments, providing a critical resource for advancing therapeutic development for this devastating liver disease.

iPSC-derived cell products

iPSC-derived Human Hepatocytes: Glycogen Storage Disease Type 1 Alpha

Cryopreserved & hydrogel-based encapsulated cells

Cryopreserved cells

Hydrogel-based encapsulated cells

Explore our Wild-Type cell products

Opti-HEP:

iPSC-derived Human Hepatocytes