Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application

Abstract Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily av...

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Autores principales: Milos Mihajlovic, Lambertus P. van den Heuvel, Joost G. Hoenderop, Jitske Jansen, Martijn J. Wilmer, Annemarie J. F. Westheim, Wil A. Allebes, Dimitrios Stamatialis, Luuk B. Hilbrands, Rosalinde Masereeuw
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:108b767fdee94ce88e5583af35dafa742021-12-02T12:31:58ZAllostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application10.1038/s41598-017-07582-12045-2322https://doaj.org/article/108b767fdee94ce88e5583af35dafa742017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07582-1https://doaj.org/toc/2045-2322Abstract Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α). A lack of direct immunogenic effect of ciPTEC was shown in co-culture experiments with peripheral blood mononuclear cells (PBMC), after appropriate stimulation of ciPTEC. Tight epithelial cell monolayer formation on polyethersulfone flat membranes was confirmed by zonula occludens-1 (ZO-1) expression in the ciPTEC tight junctions, and by restricted inulin-FITC diffusion. Co-culture with (activated) PBMC did not jeopardize the transepithelial barrier function of ciPTEC. In conclusion, the absence of allostimulatory effects and the stability of ciPTEC monolayers show that these unique cells could represent a safe option for BAK engineering application.Milos MihajlovicLambertus P. van den HeuvelJoost G. HoenderopJitske JansenMartijn J. WilmerAnnemarie J. F. WestheimWil A. AllebesDimitrios StamatialisLuuk B. HilbrandsRosalinde MasereeuwNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Milos Mihajlovic
Lambertus P. van den Heuvel
Joost G. Hoenderop
Jitske Jansen
Martijn J. Wilmer
Annemarie J. F. Westheim
Wil A. Allebes
Dimitrios Stamatialis
Luuk B. Hilbrands
Rosalinde Masereeuw
Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
description Abstract Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α). A lack of direct immunogenic effect of ciPTEC was shown in co-culture experiments with peripheral blood mononuclear cells (PBMC), after appropriate stimulation of ciPTEC. Tight epithelial cell monolayer formation on polyethersulfone flat membranes was confirmed by zonula occludens-1 (ZO-1) expression in the ciPTEC tight junctions, and by restricted inulin-FITC diffusion. Co-culture with (activated) PBMC did not jeopardize the transepithelial barrier function of ciPTEC. In conclusion, the absence of allostimulatory effects and the stability of ciPTEC monolayers show that these unique cells could represent a safe option for BAK engineering application.
format article
author Milos Mihajlovic
Lambertus P. van den Heuvel
Joost G. Hoenderop
Jitske Jansen
Martijn J. Wilmer
Annemarie J. F. Westheim
Wil A. Allebes
Dimitrios Stamatialis
Luuk B. Hilbrands
Rosalinde Masereeuw
author_facet Milos Mihajlovic
Lambertus P. van den Heuvel
Joost G. Hoenderop
Jitske Jansen
Martijn J. Wilmer
Annemarie J. F. Westheim
Wil A. Allebes
Dimitrios Stamatialis
Luuk B. Hilbrands
Rosalinde Masereeuw
author_sort Milos Mihajlovic
title Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
title_short Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
title_full Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
title_fullStr Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
title_full_unstemmed Allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
title_sort allostimulatory capacity of conditionally immortalized proximal tubule cell lines for bioartificial kidney application
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/108b767fdee94ce88e5583af35dafa74
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