title: Sandwich-cultured hepatocytes: utility for in vitro exploration of hepatobiliary drug disposition and drug-induced hepatotoxicity.
abstract: BACKGROUND
  The sandwich-cultured hepatocyte (SCH) model has become an invaluable in vitro tool for studying hepatic drug transport, metabolism, biliary excretion and toxicity. The relevant expression of many hepatocyte-specific functions together with the in vivo-like morphology favor SCHs over other preclinical models for evaluating hepatobiliary drug disposition and drug-induced hepatotoxicity.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  When human (cryopreserved) hepatocytes are used to establish sandwich cultures, the model appears particularly valuable to quantitatively investigate clinically relevant mechanisms related to in vivo 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 in vitro maintenance of the hepatocytic phenotype. Studies systematically exploring improved cell culture conditions (e.g., co-cultures or extracellular matrix modifications), as well as in vitro work identifying key transcription factors involved in hepatocyte differentiation are currently emerging.
authors: Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, O&N2, Herestraat 49-bus-921, 3000 Leuven, Belgium.
authors: Tom
authors: T
authors: De Bruyn
authors: Sagnik
authors: S
authors: Chatterjee
authors: Sarinj
authors: S
authors: Fattah
authors: Janneke
authors: J
authors: Keemink
authors: Johan
authors: J
authors: Nicolaï
authors: Patrick
authors: P
authors: Augustijns
authors: Pieter
authors: P
authors: Annaert
mesh_terms: D000818:Animals; D001659:Biliary Tract / Q000378:metabolism; D001692:Biological Transport; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology; D015925:Cryopreservation; D003470:Culture Media; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D003470:Culture Media