title: Liver and Kidney on Chips: Microphysiological Models to Understand Transporter Function.
abstract: Because of complex cellular microenvironments of both the liver and kidneys, accurate modeling of transport function has remained a challenge, leaving a dire need for models that can faithfully recapitulate both the architecture and cell-cell interactions observed in vivo. The study of hepatic and renal transport function is a fundamental component of understanding the metabolic fate of drugs and xenobiotics; however, there are few in vitro systems conducive for these types of studies. For both the hepatic and renal systems, we provide an overview of the location and function of the most significant phase I/II/III (transporter) of enzymes, and then review current in vitro systems for the suitability of a transporter function study and provide details on microphysiological systems that lead the field in these investigations. Microphysiological modeling of the liver and kidneys using "organ-on-a-chip" technologies is rapidly advancing in transport function assessment and has emerged as a promising method to evaluate drug and xenobiotic metabolism. Future directions for the field are also discussed along with technical challenges encountered in complex multiple-organs-on-chips development.
authors.affiliation: Department of Occupational and Environmental Health Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Weber
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors.forename: Kp Van
authors.initials: KV
authors.lastname: Ness
authors.affiliation: Department of Occupational and Environmental Health Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Eaton
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA. edkelly@uw.edu.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kelly
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D008658:Inactivation, Metabolic; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D046208:Microchip Analytical Procedures / Q000379:methods*; D010599:Pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins