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

J. Jansen, Ilaria De Napoli, M. Fedecostante, C.M.S. Schophuizen, Natalia Chevtchik, M. Wilmer, A.H. van Asbeck, H.J. Croes, J.C. Pertijs, F.J.M. Wetzels, L.B Hilbrands, L.P. van der Heuvel, J.G. Hoenderop, Dimitrios Stamatialis, R. Masereeuw

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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.
Original languageEnglish
Article number16702
Number of pages12
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 16 Nov 2015

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Cations
Epithelial Cells
Membranes
Kidney
Zonula Occludens-1 Protein
Histamine H2 Antagonists
Microfluidics
Tight Junctions
Cimetidine
Iodides
Confocal Microscopy
Dialysis
Perfusion
Cell Membrane

Keywords

  • METIS-313824
  • IR-99626

Cite this

Jansen, J., De Napoli, I., Fedecostante, M., Schophuizen, C. M. S., Chevtchik, N., Wilmer, M., ... Masereeuw, R. (2015). Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations. Scientific reports, 5, [16702]. https://doi.org/10.1038/srep16702
Jansen, J. ; De Napoli, Ilaria ; Fedecostante, M. ; Schophuizen, C.M.S. ; Chevtchik, Natalia ; Wilmer, M. ; van Asbeck, A.H. ; Croes, H.J. ; Pertijs, J.C. ; Wetzels, F.J.M. ; Hilbrands, L.B ; van der Heuvel, L.P. ; Hoenderop, J.G. ; Stamatialis, Dimitrios ; Masereeuw, R. / Human proximal tubule epithelial cells cultured on hollow fibers : living membranes that actively transport organic cations. In: Scientific reports. 2015 ; Vol. 5.
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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.",
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Jansen, J, De Napoli, I, Fedecostante, M, Schophuizen, CMS, Chevtchik, N, Wilmer, M, van Asbeck, AH, Croes, HJ, Pertijs, JC, Wetzels, FJM, Hilbrands, LB, van der Heuvel, LP, Hoenderop, JG, Stamatialis, D & Masereeuw, R 2015, 'Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations' Scientific reports, vol. 5, 16702. https://doi.org/10.1038/srep16702

Human proximal tubule epithelial cells cultured on hollow fibers : living membranes that actively transport organic cations. / Jansen, J.; De Napoli, Ilaria; Fedecostante, M.; Schophuizen, C.M.S.; Chevtchik, Natalia; Wilmer, M.; van Asbeck, A.H.; Croes, H.J.; Pertijs, J.C.; Wetzels, F.J.M.; Hilbrands, L.B; van der Heuvel, L.P.; Hoenderop, J.G.; Stamatialis, Dimitrios; Masereeuw, R.

In: Scientific reports, Vol. 5, 16702, 16.11.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Human proximal tubule epithelial cells cultured on hollow fibers

T2 - living membranes that actively transport organic cations

AU - Jansen, J.

AU - De Napoli, Ilaria

AU - Fedecostante, M.

AU - Schophuizen, C.M.S.

AU - Chevtchik, Natalia

AU - Wilmer, M.

AU - van Asbeck, A.H.

AU - Croes, H.J.

AU - Pertijs, J.C.

AU - Wetzels, F.J.M.

AU - Hilbrands, L.B

AU - van der Heuvel, L.P.

AU - Hoenderop, J.G.

AU - Stamatialis, Dimitrios

AU - Masereeuw, R.

N1 - Open access

PY - 2015/11/16

Y1 - 2015/11/16

N2 - 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.

AB - 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.

KW - METIS-313824

KW - IR-99626

U2 - 10.1038/srep16702

DO - 10.1038/srep16702

M3 - Article

VL - 5

JO - Scientific reports

JF - Scientific reports

SN - 2045-2322

M1 - 16702

ER -