Three new papers confirm the OrganoPlate® as the platform of choice for nephrotoxicity screenings
In vitro kidney models that accurately represent in vivo kidney functions are difficult to come by. Nephrons of kidneys are highly polarized structures which require 3D cell culture to grow in vitro. Without polarization of kidney tissue and physiological drug-transporter interactions, reliable nephrotoxicity tests of novel drugs are difficult to establish. As such, it is crucial to implement polarization in in vitro kidney models.
Three recent publications in The AAPS Journal successfully used MIMETAS OrganoPlate® to build a robust platform for nephrotoxicity screenings by modeling the Renal Proximal Tubule on a chip. The model showed gene expression of various relevant drug transporters. Furthermore, two types of transporters, P-gp and MRP2/4, demonstrated to be functionally active in the tubules, indicating the establishment of a basolateral and an apical membrane (Vriend, 2018; Vormann, 2018). The epithelial barrier could be disrupted by exposure of the tubules to the nephrotoxic cisplatin, leading to a decrease in cell viability and tubule function (Vormann, 2018). Lastly, the model has been used to establish novel markers for cell viability. After nephrotoxic treatment, several miRNAs were upregulated and indicative of proximal tubule damage. Interestingly, these markers outperformed existing viability assessment techniques such as the WWST-8 assay and NAG (Suter-Dick, 2018).
These findings indicate that kidney tubules on-a-chip provide a robust, high-throughput cell culture that allows accurate assessment of nephrotoxicity.
Written by Indi Joore
Suter-Dick, L., Mauch, L., Ramp, D., Caj, M., Vormann, M. K., Hutter, S., ... & Wilmer, M. J. (2018). Combining extracellular miRNA determination with microfluidic 3D cell cultures for the assessment of nephrotoxicity: a proof of concept study. The AAPS Journal, 20(5), 86.
Vormann, M. K., Gijzen, L., Hutter, S., Boot, L., Nicolas, A., van den Heuvel, A., ... & de Wagenaar, B. (2018). Nephrotoxicity and kidney transport assessment on 3D perfused proximal tubules. The AAPS Journal, 20(5), 90.
Vriend, J., Nieskens, T. T., Vormann, M. K., van den Berge, B. T., van den Heuvel, A., Russel, F. G., ... & Wilmer, M. J. (2018). Screening of drug-transporter interactions in a 3D microfluidic renal proximal tubule on a chip. The AAPS Journal, 20(5), 87.