Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 790, Issue -, Pages 28-35Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2016.07.009
Keywords
Bioartificial kidney device; Living membrane; Functionalized hollow fiber membranes; Conditionally immortalized human renal; proximal tubule epithelial cells; Monolayer of functional cells
Categories
Funding
- EU Marie Curie ITN Project BIOART [316690]
- EU Marie Curie ITN Project BIOART (EU-FP7-PEOPLE-ITN)
- EUTox Working Group, of the European society of European Society for artificial organs
- BioNanoLab of the University of Twente, the Netherlands
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The limited removal of metabolic waste products in dialyzed kidney patients leads to high morbidity and mortality. One powerful solution for a more complete removal of those metabolites might be offered by a bioartificial kidney device (BAK), which contains a hybrid living membrane with functional proximal tubule epithelial cells (PTEC). These cells are supported by an artificial functionalized hollow fiber membrane (HFM) and are able to actively remove the waste products. In our earlier studies, conditionally immortalized human PTEC (ciPTEC) showed to express functional organic cationic transporter 2 (OCT2) when seeded on small size flat or hollow fiber polyethersulfone (PES) membranes. Here, an upscaled living membrane is presented. We developed and assessed the functionality of modules containing three commercially available MicroPES HFM supporting ciPTEC. The HFM were optimally coated with L-Dopa and collagen IV to support a uniform and tight monolayer formation of matured ciPTEC under static culturing conditions. Both abundant expression of zonula occludens-1 (ZO-1) protein and limited diffusion of FITC-inulin confirm a clear barrier function of the monolayer. Furthermore, the uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)), a fluorescent OCT2 substrate, was studied in absence and presence of known OCT inhibitors, such as cimetidine and a cationic uremic solutes mixture. The ASP(+) uptake by the living upscaled membrane was decreased by 60% in the presence of either inhibitor, proving the active function of OCT2. In conclusion, this study presents a successful upscaling of a living membrane with active organic cation transport as a support for BAK device. (C) 2016 Elsevier B.V. All rights reserved.
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