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Upscaling of a living membrane for bioartificial kidney device.

Abstract：

: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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Chevtchik NV,Fedecostante M,Jansen J,Mihajlovic M,Wilmer M,Rüth M,Masereeuw R,Stamatialis D

doi

10.1016/j.ejphar.2016.07.009

subject

Has Abstract

pub_date

2016-11-05 00:00:00

pages

28-35

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(16)30439-3

journal_volume

790

pub_type

杂志文章

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