Abstract

LiverChip – Development of Organ-on-a-chip Liver Disease Models

David Hughes, Chief Technical Officer, CN Bio Innovations Ltd

Organ-on-a-chip (OOC) technologies offer the promise of in vitro models which more closely recapitulate the in vivo. Current OOCs typically have low to medium throughput, offer high information content and are relatively complex when compared to 2D cultures, making it more likely that these technologies could replace certain animal tests than supplant high throughput screens. An initial wave of activity focused on drug metabolism and safety applications of OOCs however an animal-centric regulatory framework, particularly for safety testing, and a disconnect between the cost and benefit that OOCs can provide in ADME/Tox make this a challenging area in which to achieve widespread adoption. Disease modelling provides a more compelling opportunity for OOC technologies: a number of diseases are poorly recapitulated in animal models so OOCs offering improved translational relevance would be highly desirable.  A small airway-on-a-chip to model COPD and asthma, and a hepatitis B infected liver-on-a-chip model are two examples of disease OOCs already being exploited by pharmaceutical companies in the development of new drugs. This presentation will describe the development of models for viral hepatitis, malaria and non-alcoholic fatty liver disease (NAFLD) building on a microfluidic OOC platform, LiverChip®.  Liver disease represents a significant and growing global health burden, being the only one of the top five causes of death to have increased in the UK in the last decade. The liver is a complex organ, comprised of multiple cell types undertaking hundreds of essential functions and is a major site of drug metabolism and toxicity. The liver is also a unique immunological organ in which liver resident macrophage (Kupffer) cells and lymphocytes play critical roles in first line immune defence against invading pathogens, modulation of liver injury and recruitment of circulating lymphocytes.  LiverChip® disease models are based on cryopreserved primary human h