For regulatory submissions in the development of drugs for topical administration, a pharmaceutical company will use around 1,000 animals in studies relating to skin toxicity per year- approximately 30% of which involve non-rodent species, in particular, the minipig. Novel modelling approaches developed though this Challenge will reduce and replace significant numbers of animals and where animals are still used, minimise the number of required time points/doses.
The team at Newcells Biotech Ltd led by Professor Lyle Armstrong propose a human skin model of metabolism that will be developed from skin cells derived from human induced pluripotent stem cells (hiPSC) and layered into a full thickness representation of human skin. Their model will include fibroblasts, monocytes and macrophages in the dermal layer with keratinocytes and dendritic cells in the epidermal layer. To develop the hiPSC derived assay and the in-silico skin metabolism model, human skin will be examined for structural, genetic, proteomic and metabolic composition to provide the parameters needed to produce both models. The hiPSC derived skin model of metabolism will be evaluated by its ability to metabolise chemicals in the same way as human skin.
The computational modelling system will simulate the spatio-temporal perfusion of xenochemicals in heterogeneous skin tissue and the subsequent metabolism of those chemicals within skin cells. The model itself will be open source, issued under a permissive Creative Commons (CC) public copyright licence and will be validated using data from the laboratory experiments.
Full details about this CRACK IT Challenge can be found on the CRACK IT website.