期刊
KIDNEY INTERNATIONAL
卷 90, 期 3, 页码 627-637出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2016.06.011
关键词
cell polarity; cell survival; proximal tubule
资金
- National Center for Advancing Translational Sciences of the National Institutes of Health [TL1TR000422, KL2 TR000421, UH2/UH3TR000504]
- University of Washington Drug Metabolism, Transport, and Pharmacogenomic Research program
- Northwest Kidney Centers
- U.S. Environmental Protection Agency [83573801]
- Norman S. Coplon Extramural Grant Program by Satellite Healthcare
- Warren G. Magnuson Scholarship at the University of Washington
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.
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