Sandwich-cultured hepatocytes: utility for in vitro exploration of hepatobiliary drug disposition and drug-induced hepatotoxicity. (May 2013)

• Record Type: Journal Article
• Authors: De Bruyn, Tom; Chatterjee, Sagnik; Fattah, Sarinj; Keemink, Janneke; Nicolaï, Johan; Augustijns, Patrick; Annaert, Pieter
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 9:Number 5(2013:May)
• Page Start: 589
• Page End: 616
• Publication Date: 2013-05
• Subjects: Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1517/17425255.2013.773973
• Languages: English
• ISSNs: 1742-5255

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> The sandwich-cultured hepatocyte (SCH) model has become an invaluable <italic>in vitro</italic> tool for studying hepatic drug transport, metabolism, biliary excretion and toxicity. The relevant expression of many hepatocyte-specific functions together with the <italic>in vivo</italic>-like morphology favor SCHs over other preclinical models for evaluating hepatobiliary drug disposition and drug-induced hepatotoxicity.</p> <p> <bold> <italic>Areas covered:</italic> </bold> In this review, the authors highlight recommended procedures required for reproducibly culturing hepatocytes in sandwich configuration. It also provides an overview of the SCH model characteristics as a function of culture time. Lastly, the article presents a summary of the most prominent applications of the SCH model, including hepatic drug clearance prediction, drug–drug interaction potential and drug-induced hepatotoxicity.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> When human (cryopreserved) hepatocytes are used to establish sandwich cultures, the model appears particularly valuable to quantitatively investigate clinically relevant mechanisms related to <italic>in vivo</italic> hepatobiliary drug disposition and hepatotoxicity. Nonetheless, the SCH model would largely benefit from better insight into the fundamental cell signaling mechanisms that are critical for long-term <italic>in vitro</italic> maintenance of the hepatocytic phenotype. Studies systematically exploring improved cell culture conditions (e.g., co-cultures or extracellular matrix modifications), as well as <italic>in vitro</italic> work identifying key transcription factors involved in hepatocyte differentiation are currently emerging.</p> </abstract>