title: Bioengineered kidney tubules efficiently excrete uremic toxins.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Physiology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Department of Pediatrics, Radboud university medical center, Nijmegen, The Netherlands.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Jansen
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Physiology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Department of Pediatrics, Radboud university medical center, Nijmegen, The Netherlands.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Fedecostante
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wilmer
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Peters
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: U M
authors.initials: UM
authors.lastname: Kreuser
authors.affiliation: Department of Pharmacology and Toxicology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: van den Broek
authors.affiliation: Cluster for Molecular Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Mensink
authors.affiliation: Cluster for Molecular Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: Boltje
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Stamatialis
authors.affiliation: Nephrology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Wetzels
authors.affiliation: Department of Pediatrics, Radboud university medical center, Nijmegen, The Netherlands.|Department of Pediatric Nephrology &Growth and Regeneration, Catholic University Leuven, Leuven, Belgium.
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.affiliation: Physiology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Hoenderop
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Masereeuw
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism*; D023822:Tissue Engineering
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D027362:Organic Anion Transport Protein 1; C073492:ABCC4 protein, human; C116614:ABCG2 protein, human