Urine derived human cells as model systems in drug discovery and toxicology


Johannes Grillari1,3, Lukas Fliedl2, Alice Limonciel4, Walter Pfaller4, Matthias Wieser2,3 Paul Jennings4, Miguel Esteban5, Duanqing Pei5,and Regina Grillari-Voglauer1,2,4

1 Christian Doppler Laboratory on Biotechnology of Skin Aging, Dept. of Biotechnology, Universität für Bodenkultur Wien, Austria; 2 Austrian Center for Industrial Biotechnology, Vienna 3 Evercyte GmbH, Vienna, Austria; 4 Medical University Innsbruck, Austria, 5 Chinese Academy of Sciences, Guangzhou, China

Nephrotoxicity of chemicals or therapeutics can be caused by damage to all parts of the kidney including glomeruli and the tubuli. As many biomarkers of acute and chronic nephropathy depend on enzymes and proteins found in urine that derive from the proximal tubuli, proximal tubular injury seems to be an event of prime importance.
Therefore, establishing human proximal tubular epithelial cell cultures is necessary for nephrotoxicity testing and for screening of kidney protective substances that e.g. can be co-administered during chemotherapeutic treatment of cancer patients to diminish kidney injury.
So far, the short replicative life span and the limited access to human RPTECs has limited their use in the field of in vitro toxicology. We recently established the telomerase immortalized renal proximal tubular epithelial cells from tissue and alternatively also from urine as a non-invasive source of cells. The cells were used as a model system to study cisplatin nephrotoxicity.
In addition, we were able to reprogram these cells to induced pluripotent stem cells and differentiate them to cardiomyocyte, hepatocyte and neuronal lineages. Thus, urine derived cells represent a novel non-invasive source of human, primary like cells that represent relevant and standardizable model system in drug discovery and toxicology, as well as in all fields of pharmaceutical, chemical and cosmetic industries.

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