Applications

• Cardiac safety pharmacology and proarrhythmia screening

• Structural cardiotoxicity assessment for oncology compounds

• Donor-stratified and sex-stratified cardiac risk panels

• Cardiac disease modelling

• Co-culture with iPSC-derived cardiac fibroblasts

• High-content imaging and phenotypic profiling

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

Shared donor library

Cardiomyocytes draw on the same HLA-typed, ancestrally diverse iPSC library documented for the Cytochroma hepatic range, with 71 distinct HLA alleles across 8 fully typed lines and pairwise mismatch scores of 7 to 10 out of 10 between almost every donor pair.

Medicines Discovery catapult

Cytochroma was awarded an Innovate UK grant to develop multicellular cardiac models composed of cardiomyocytes (CM), endothelial cells (E) and fibroblasts (F) combined known as CMEFs. These were more accurately able to predict toxicity due to multiple cell types present, by using iPS derived cells there is no need for variable primary cells adding an additional layer of biological complexity. 'Mix and match' different donors to examine HLA target effects.