Applications

• Drug-induced liver injury (DILI) and hepatotoxicity screening

• MAFLD and MASH disease modelling with quantifiable steatosis by high-content imaging

• Cytochrome P450 induction, inhibition and metabolic stability studies

• Hepatic transporter and efflux studies in polarised cells

• Ancestry-stratified and donor-specific toxicity panels for AI drug discovery

• Cell Painting and multiplexed high-content phenotypic profiling

• 3D microtissue and co-culture models with Kupffer cells and hepatic stellate cells

Donor diversity and HLA typing

Every Cytochroma cell model is differentiated from an induced pluripotent stem cell library built deliberately for population-level variability rather than convenience. 8 of 18 of 18 iPSC donor lines fully HLA-typed at two-field resolution. 71 distinct HLA alleles across the panel. 1:1 female to male donor balance. European, Native American and African ancestry represented. Pairwise HLA mismatch scores of 7 to 10 out of 10 between almost every donor pair, across HLA-A, B, C, DRB1 and DQB1.

Typing covers the classical class I loci HLA-A, HLA-B and HLA-C and the class II loci DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1 at two-field resolution. Full multi-field typing is available on request. Because almost every donor pair scores 7 to 10 out of 10 on pairwise allele-level mismatch, donor-mismatched co-culture, allogeneic response and HLA-restriction studies can be set up off the shelf.

Evidence and validation

Peer-reviewed MASH application

Lipid-loaded Cytochroma hepatocytes recapitulated the transcriptional and metabolic dysregulation of MAFLD/MASH, discriminated target-selective Cyclophilin B over Cyclophilin A inhibitors, and gave compound potency comparable to FDA-approved resmetirom. Published as Optimization of Cyclophilin B-Targeted Tri-vector Inhibitors for Novel MASH Treatments, Journal of Medicinal Chemistry 2025, 68(6), 6815 (DOI 10.1021/acs.jmedchem.5c00301), with the University of Edinburgh.

Automated functional validation

Line MAN-010-2H was differentiated and benchmarked through a fully automated high-content screening workflow at a specialist contract research partner: 97.9% post-thaw viability, a multiplexed Cell Painting assay resolving distinct mechanisms of toxicity across a panel of 8 compounds, and a stable staurosporine dose-response from 12 to 48 hours (pIC50 5.3 to 6.2, signal-to-background 2.55). Automated seeding roughly halved well-to-well assay variability.

Multi-donor CYP450 profiling

Diverse-donor iHeps express key CYP450 enzymes with functionally relevant induction and reproducible donor-dependent variability, unlike HepG2 or short-lived primary hepatocytes.

Consortium participation

Cytochroma is the Advanced Liver Partner to the HESI OASIS consortium, convened by HESI Global and the Broad Institute of Harvard and MIT, contributing diverse-donor human liver models to its hepatic-safety programme.

“Their hepatocyte MASH models helped us quickly evaluate novel inhibitors in a biologically relevant model, essential data for our J. Med. Chem. publication.”

Dr Dahlia Doughty-Shenton, University of Edinburgh

OASIS Consortium

Cytochroma is an Advanced Liver Partner in the OASIS Consortium (’Omics for Assessing Signatures for Integrated Safety), a pre-competitive hepatic-safety consortium convened in July 2023 by HESI Global and the Broad Institute of Harvard and MIT as a working group of HESI’s eSTAR committee. OASIS integrates transcriptomics, proteomics and high-content Cell Painting across human-relevant models, with an initial focus on liver safety, and spans more than 160 experts across 17 academic institutes, 7 government agencies, 17 industry organisations and 3 NGOs. Cytochroma contributes diverse-donor human liver models to the consortium’s hepatic-safety programme. See The OASIS Consortium: Integrating Multi-Omics Technologies to Transform Chemical Safety Assessment, Rouquié et al., Toxicological Sciences 2025, 208(2), 225 (DOI 10.1093/toxsci/kfaf128).