A bioartificial kidney device with polarized secretion of immune modulators

Journal of Tissue Engineering and Regenerative Medicine
N V ChevtchikD Stamatialis

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 ...Continue Reading

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Citations

Oct 31, 2019·Archives of Toxicology·João FariaRosalinde Masereeuw
Nov 30, 2018·Tissue Engineering. Part a·Harold D LoveWilliam H Fissell
Aug 12, 2021·Clinical and Translational Science·Kirk P Van NessEdward J Kelly

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