Objective

Pre-clinical efficacy and toxicology data derived from in vitro and animal models often fails to translate to clinical trials, resulting in high rates of attrition and falling R&D productivity. Consequently, the development of more predictive in vitro systems represents one of the most urgent challenges currently facing the bio-pharmaceutical industry. To this end, we are currently developing a novel platform for the assessment of stem cell-derived epithelial function in vitro, initially developed for respiratory applications but ultimately applicable to any epithelium. The platform is based on a recently developed 3D model of human airway epithelium grown within a microfluidic chip that simulates the circulation of fluids in tissue and enables the analysis of key physiological, biochemical and phenotypic outputs. Importantly, when challenged, epithelial layers grown on the system display previously unseen cytokine responses. By delivering more predictive data, the system has huge potential to impact pre-clinical drug discovery, chemical safety testing and safety pharmacology. Here, we present an overview of the technology and data illustrating our progress in the development of an optimised cell culture regimen designed to generate functional respiratory epithelia from induced pluripotent stem cells (IPSCs).