Bioengineered kidney tubules efficiently excrete uremic toxins

Jitske Jansen, M. Fedecostante, M. Wilmer, J.G. Peters, U.M. Kreuser, P.H. Broek, R.A. Mensink, T.J. Boltje, Dimitrios Stamatialis, J.F. Wetzels, L.P. van der Heuvel, J.G. Hoenderop, R. Masereeuw

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Abstract

The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs.
Original languageEnglish
Article number26715
JournalScientific reports
Volume6
Issue number26715
DOIs
Publication statusPublished - 2016

Fingerprint

Kidney Tubules
Kidney
Indican
BRCA1 Protein
Organic Anion Transporters
Kynurenic Acid
P-Glycoproteins
Waste Products
Regenerative Medicine
Renal Replacement Therapy
Serum Albumin
Chronic Kidney Failure
Blood Proteins
Albumins
Epithelial Cells
Pharmaceutical Preparations
Therapeutics

Keywords

  • METIS-318788
  • IR-103649

Cite this

Jansen, J., Fedecostante, M., Wilmer, M., Peters, J. G., Kreuser, U. M., Broek, P. H., ... Masereeuw, R. (2016). Bioengineered kidney tubules efficiently excrete uremic toxins. Scientific reports, 6(26715), [26715]. https://doi.org/10.1038/srep26715
Jansen, Jitske ; Fedecostante, M. ; Wilmer, M. ; Peters, J.G. ; Kreuser, U.M. ; Broek, P.H. ; Mensink, R.A. ; Boltje, T.J. ; Stamatialis, Dimitrios ; Wetzels, J.F. ; van der Heuvel, L.P. ; Hoenderop, J.G. ; Masereeuw, R. / Bioengineered kidney tubules efficiently excrete uremic toxins. In: Scientific reports. 2016 ; Vol. 6, No. 26715.
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Jansen, J, Fedecostante, M, Wilmer, M, Peters, JG, Kreuser, UM, Broek, PH, Mensink, RA, Boltje, TJ, Stamatialis, D, Wetzels, JF, van der Heuvel, LP, Hoenderop, JG & Masereeuw, R 2016, 'Bioengineered kidney tubules efficiently excrete uremic toxins' Scientific reports, vol. 6, no. 26715, 26715. https://doi.org/10.1038/srep26715

Bioengineered kidney tubules efficiently excrete uremic toxins. / Jansen, Jitske; Fedecostante, M.; Wilmer, M.; Peters, J.G.; Kreuser, U.M.; Broek, P.H.; Mensink, R.A.; Boltje, T.J.; Stamatialis, Dimitrios; Wetzels, J.F.; van der Heuvel, L.P.; Hoenderop, J.G.; Masereeuw, R.

In: Scientific reports, Vol. 6, No. 26715, 26715, 2016.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Jansen, Jitske

AU - Fedecostante, M.

AU - Wilmer, M.

AU - Peters, J.G.

AU - Kreuser, U.M.

AU - Broek, P.H.

AU - Mensink, R.A.

AU - Boltje, T.J.

AU - Stamatialis, Dimitrios

AU - Wetzels, J.F.

AU - van der Heuvel, L.P.

AU - Hoenderop, J.G.

AU - Masereeuw, R.

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AB - The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs.

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Jansen J, Fedecostante M, Wilmer M, Peters JG, Kreuser UM, Broek PH et al. Bioengineered kidney tubules efficiently excrete uremic toxins. Scientific reports. 2016;6(26715). 26715. https://doi.org/10.1038/srep26715