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

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) h...

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Autores principales: Jansen, J., De Napoli, I. E, Fedecostante, M., Schophuizen, C. M. S., Chevtchik, N. V., Wilmer, M. J., van Asbeck, A. H., Croes, H. J., Pertijs, J. C., Wetzels, J. F. M., Hilbrands, L. B., van den Heuvel, L. P., Hoenderop, J. G., Stamatialis, D., Masereeuw, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644946/
https://www.ncbi.nlm.nih.gov/pubmed/26567716
http://dx.doi.org/10.1038/srep16702
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author Jansen, J.
De Napoli, I. E
Fedecostante, M.
Schophuizen, C. M. S.
Chevtchik, N. V.
Wilmer, M. J.
van Asbeck, A. H.
Croes, H. J.
Pertijs, J. C.
Wetzels, J. F. M.
Hilbrands, L. B.
van den Heuvel, L. P.
Hoenderop, J. G.
Stamatialis, D.
Masereeuw, R.
author_facet Jansen, J.
De Napoli, I. E
Fedecostante, M.
Schophuizen, C. M. S.
Chevtchik, N. V.
Wilmer, M. J.
van Asbeck, A. H.
Croes, H. J.
Pertijs, J. C.
Wetzels, J. F. M.
Hilbrands, L. B.
van den Heuvel, L. P.
Hoenderop, J. G.
Stamatialis, D.
Masereeuw, R.
author_sort Jansen, J.
collection PubMed
description 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.
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spelling pubmed-46449462015-11-20 Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations Jansen, J. De Napoli, I. E Fedecostante, M. Schophuizen, C. M. S. Chevtchik, N. V. Wilmer, M. J. van Asbeck, A. H. Croes, H. J. Pertijs, J. C. Wetzels, J. F. M. Hilbrands, L. B. van den Heuvel, L. P. Hoenderop, J. G. Stamatialis, D. Masereeuw, R. Sci Rep Article 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. Nature Publishing Group 2015-11-16 /pmc/articles/PMC4644946/ /pubmed/26567716 http://dx.doi.org/10.1038/srep16702 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Jansen, J.
De Napoli, I. E
Fedecostante, M.
Schophuizen, C. M. S.
Chevtchik, N. V.
Wilmer, M. J.
van Asbeck, A. H.
Croes, H. J.
Pertijs, J. C.
Wetzels, J. F. M.
Hilbrands, L. B.
van den Heuvel, L. P.
Hoenderop, J. G.
Stamatialis, D.
Masereeuw, R.
Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title_full Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title_fullStr Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title_full_unstemmed Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title_short Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
title_sort human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644946/
https://www.ncbi.nlm.nih.gov/pubmed/26567716
http://dx.doi.org/10.1038/srep16702
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