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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2017
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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) |
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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 |
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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 |
work_keys_str_mv |
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