Abstract

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). Human biological samples
used for this project were sourced ethically and their research use was in
accord with the terms of the informed consents.