A bioartificial kidney device with polarized secretion of immune modulators

N. V. Chevtchik, M. Mihajlovic, M. Fedecostante, L. Bolhuis-Versteeg, J. Sastre Toraño, R. Masereeuw, D. Stamatialis* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
88 Downloads (Pure)

Abstract

The accumulation of protein-bound toxins in dialyzed patients is strongly associated with their high morbidity and mortality. The bioartificial kidney device (BAK), containing proximal tubule epithelial cells (PTECs) seeded on functionalized synthetic hollow fibre membranes, may be a powerful solution for the active removal of those metabolites. In an earlier study, we developed an upscaled BAK containing conditionally immortalized human PTEC with functional organic cationic transporter 2. Here, we first extended this development to a BAK device having cells with the organic anionic transporter 1, capable of removing anionic uraemic wastes. We confirmed the quality of the conditionally immortalized human PTEC monolayer by confocal microscopy and paracellular inulin-fluorescein isothiocyanate leakage, as well as by the active transport of anionic toxin, indoxyl sulphate. Furthermore, we assessed the immune safety of our system by measuring the production of relevant cytokines by the cells after lipopolysaccharide stimulation. Upon lipopolysaccharide treatment, we observed a polarized secretion of proinflammatory cytokines by the cells: 10-fold higher in the extraluminal space, corresponding to the urine compartment, as compared with the intraluminal space, corresponding to the blood compartment. To the best of our knowledge, our work is the first to show this favourable cell polarization in a BAK upscaled device.

Original languageEnglish
Pages (from-to)1670-1678
Number of pages9
JournalJournal of tissue engineering and regenerative medicine
Volume12
Issue number7
Early online date15 May 2018
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • UT-Hybrid-D
  • ciPTEC monolayer
  • living membrane
  • organic anionic transporter
  • polarized secretion of immune modulators
  • bioartificial kidney

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