A morphological and functional comparison of proximal tubule cell lines established from human urine and kidney tissue.

3566's picture
Journal Title, Volume, Page: 
Exp Cell Res. 2014 Apr 15;323(1):87-99. doi: 10.1016/j.yexcr.2014.02.011.
Year of Publication: 
2014
Authors: 
J. Jansen
Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Pediatrics, Radboud University Medical Center, The Netherlands
C.M.S. Schophuizen
Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands. . Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Pediatrics, Radboud University Medical Center, The Netherlands
M.J. Wilmer
Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands
Saad Al-Lahham
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Current Affiliation: 
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah University, Nablus, Palestine.
and others please look to the link
Preferred Abstract (Original): 

Promising renal replacement therapies include the development of a bioartificial kidney using functional human kidney cell models. In this study, human conditionally immortalized proximal tubular epithelial cell (ciPTEC) lines originating from kidney tissue (ciPTEC-T1 and ciPTEC-T2) were compared to ciPTEC previously isolated from urine (ciPTEC-U).

Subclones of all ciPTEC isolates formed tight cell layers on Transwell inserts as determined by transepithelial resistance, inulin diffusion, E-cadherin expression and immunocytochemisty. Extracellular matrix genes collagen I and -IV α1 were highly present in both kidney tissue derived matured cell lines (p<0.001) compared to matured ciPTEC-U, whereas matured ciPTEC-U showed a more pronounced fibronectin I and laminin 5 gene expression (p<0.01 and p<0.05, respectively). Expression of the influx carrier Organic Cation Transporter 2 (OCT-2), and the efflux pumps P-glycoprotein (P-gp), Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance Protein (BCRP) were confirmed in the three cell lines using real-time PCR and Western blotting. The activities of OCT-2 and P-gp were sensitive to specific inhibition in all models (p<0.001). The highest activity of MRP4 and BCRP was demonstrated in ciPTEC-U (p<0.05). Finally, active albumin reabsorption was highest in ciPTEC-T2 (p<0.001), while Na+-dependent phosphate reabsorption was most abundant in ciPTEC-U (p<0.01).

In conclusion, ciPTEC established from human urine or kidney tissue display comparable functional PTEC specific transporters and physiological characteristics, providing ideal human tools for bioartificial kidney development.