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Kidney Int. 2016 Sep;90(3):627-37. doi: 10.1016/j.kint.2016.06.011.

Development of a microphysiological model of human kidney proximal tubule function.

Author information

1
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
2
Department of Pharmacy, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA.
3
Department of Biological Structure, University of Washington, Seattle, Washington, USA.
4
Nortis Inc., Seattle, Washington, USA.
5
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA; Department of Pharmacy, University of Washington, Seattle, Washington, USA.
6
Department of Medicine, University of Washington, Seattle, Washington, USA.
7
Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA. Electronic address: himmej@u.washington.edu.
8
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA. Electronic address: edkelly@uw.edu.

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.

KEYWORDS:

cell polarity; cell survival; proximal tubule

PMID:
27521113
PMCID:
PMC4987715
DOI:
10.1016/j.kint.2016.06.011
[Indexed for MEDLINE]
Free PMC Article

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