Imaging Bile Canaliculi in 3D Liver Microtissues using the Opera Phenix High Content Screening System
Abstract: Analyzing transport of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. A functional impairment of hepatobilary transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP-2), is strongly associated with an increased risk of cholestatic liver injury. Currently, artificial models, such as BSEP expressing membrane vesicles, are used for studying efflux transporter function. Sandwich-cultured hepatocytes also are utilized as an in vitro tool to study hepatobiliary drug transport and hepatotoxicity [Lepist et al., 2014]. However, these models lack the functional complexity of the natural 3-dimensional (3D) liver environment. 3D liver cells immediately display key morphological and functional characteristics of native hepatocytes, such ascuboidal cell shape, increased formation of bile canaliculi and higher drug efflux activity, compared to the conventional monolayer culture [Hammad et al., 2014; Mueller et al., 2011].