title: Development of a microphysiological model of human kidney proximal tubule function.
abstract: The kidney proximal tubule is the primary site in the nephron for excretion of waste products through a combination of active uptake and secretory processes and is also a primary target of drug-induced nephrotoxicity. Here, we describe the development and functional characterization of a 3-dimensional flow-directed human kidney proximal tubule microphysiological system. The system replicates the polarity of the proximal tubule, expresses appropriate marker proteins, exhibits biochemical and synthetic activities, as well as secretory and reabsorptive processes associated with proximal tubule function in vivo. This microphysiological system can serve as an ideal platform for ex vivo modeling of renal drug clearance and drug-induced nephrotoxicity. Additionally, this novel system can be used for preclinical screening of new chemical compounds prior to initiating human clinical trials.
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Elijah J
authors: EJ
authors: Weber
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Alenka
authors: A
authors: Chapron
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Brian D
authors: BD
authors: Chapron
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Jenna L
authors: JL
authors: Voellinger
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Kevin A
authors: KA
authors: Lidberg
authors: Department of Pharmacy, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA.
authors: Catherine K
authors: CK
authors: Yeung
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Zhican
authors: Z
authors: Wang
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Yoshiyuki
authors: Y
authors: Yamaura
authors: Department of Biological Structure, University of Washington, Seattle, Washington, USA.
authors: Dale W
authors: DW
authors: Hailey
authors: Nortis Inc., Seattle, Washington, USA.
authors: Thomas
authors: T
authors: Neumann
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA; Department of Pharmacy, University of Washington, Seattle, Washington, USA.
authors: Danny D
authors: DD
authors: Shen
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
authors: Kenneth E
authors: KE
authors: Thummel
authors: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Kimberly A
authors: KA
authors: Muczynski
authors: Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA. Electronic address: himmej@u.washington.edu.
authors: Jonathan
authors: J
authors: Himmelfarb
authors: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA. Electronic address: edkelly@uw.edu.
authors: Edward J
authors: EJ
authors: Kelly
mesh_terms: D001693:Biological Transport, Active; D018929:Cell Culture Techniques; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D008954:Models, Biological; D065667:Renal Elimination / Q000502:physiology*
keywords: cell polarity; cell survival; proximal tubule