Modeling Human Kidney Biology
Nephrotoxicity is of increasing concern in the drug development pipeline and the kidney proximal tubule is the primary site of renal toxicity. Conventional preclinical renal assays, such as in vitro cell culture and animal models, often fail to accurately model the complexity of organ toxicity seen in drug responses due to limited functionality or species-specific variation.
ExVive™ Human Kidney Tissue is a fully human 3D bioprinted tissue comprised of an apical layer of polarized primary renal proximal tubule epithelial cells (RPTECs) supported by a collagen IV-rich tubulointerstitial interface of primary renal fibroblasts and endothelial cells.
Tissues are printed under stringent quality controlled conditions and are designed to model native biology and architecture in a highly reproducible manner for optimal preservation of cellular function and transporter activity. Epithelial cells form tight junctions and maintain stable gamma glutamyl-transferase activity and native renal transporter expression for multiple weeks in culture.
The cellular and architectural structure of ExVive™ Human Kidney Tissue provides an ideal means to study the many phenotypes of nephrotoxicity including tubular transport of xenobiotics, proteins, and ions.
- Composition and architecture enables the biochemical and histological assessment of human renal toxicity.
- Tissue-like complexity supports the detection of injury, compensation, and recovery.
- Physiological expression of transporters models native transport activity.
Cisplatin is a widely used chemotherapeutic that is well characterized as a nephrotoxicant with multiple modes of action. On its path towards excretion, cisplatin is taken up by RPTECs via transporters such as OCT2. Upon accumulation of cisplatin in the epithelial cells, reactive oxygen species and toxic glutathione conjugates are formed resulting in cell damage and subsequent renal toxicity. Cimetidine, an OCT2 inhibitor, can block the accumulation of cisplatin and the ensuing tissue damage.
Cisplatin-mediated nephrotoxicity and its prevention by cimetidine was shown in ExVive™ Human Kidney Tissue.
- Tissues are treated for 7 days with increasing doses of cisplatin.
- Dose-dependent decrease in overall tissue viability (Resazurin) and epithelial-specific viability (GGT) is observed.
- Biomarkers for renal toxicity, Clusterin and NGAL, are detected in response to insult.
- Inhibition of OCT2 by cimetidine effectively blocks cisplatin-induced toxicity.
NovoView™ Preclinical Safety Testing Services
ExVive™ 3D Bioprinted Kidney Tissues are available through our NovoView™ Preclinical Safety Testing Services that are designed specifically to meet your study requirements. We work closely with you to design an optimal combination of biochemical and histological readouts to assess the physiologically-relevant effects of your compound on human tissues.
At Organovo, we apply state of the art quality control and assurance processes to ensure that our customers can rely on the quality and reproducibility of the data we generate. Our tissue team has years of experience in every step of the bioprinting process, from bioprinting itself to subsequent maintenance, monitoring, and analyses of the ExVive™ Human Kidney Tissues.
Our dedicated team of scientific experts provide comprehensive consultation to determine which parameters best suit your needs.