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Sci Rep. 2015 Nov 16;5:16702. doi: 10.1038/srep16702.

Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations.

Author information

1
Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
2
Department of Physiology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
3
Department of Pediatrics, Radboud university medical center, Nijmegen, The Netherlands.
4
Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands.
5
Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
6
Department of Cell Biology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
7
Department of Nephrology, Radboud university medical center, Nijmegen, The Netherlands.
8
Department of Pediatric Nephrology &Growth and Regeneration, Catholic University Leuven, Leuven, Belgium.
9
Div. Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, The Netherlands.

Abstract

The bioartificial kidney (BAK) aims at improving dialysis by developing 'living membranes' for cells-aided removal of uremic metabolites. Here, unique human conditionally immortalized proximal tubule epithelial cell (ciPTEC) monolayers were cultured on biofunctionalized MicroPES (polyethersulfone) hollow fiber membranes (HFM) and functionally tested using microfluidics. Tight monolayer formation was demonstrated by abundant zonula occludens-1 (ZO-1) protein expression along the tight junctions of matured ciPTEC on HFM. A clear barrier function of the monolayer was confirmed by limited diffusion of FITC-inulin. The activity of the organic cation transporter 2 (OCT2) in ciPTEC was evaluated in real-time using a perfusion system by confocal microscopy using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) as a fluorescent substrate. Initial ASP(+) uptake was inhibited by a cationic uremic metabolites mixture and by the histamine H2-receptor antagonist, cimetidine. In conclusion, a 'living membrane' of renal epithelial cells on MicroPES HFM with demonstrated active organic cation transport was successfully established as a first step in BAK engineering.

PMID:
26567716
PMCID:
PMC4644946
DOI:
10.1038/srep16702
[Indexed for MEDLINE]
Free PMC Article

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