At present, it is however not possible to completely replace animal testing. This is especially true when testing the effects of repeated doses over longer periods of time.
A SEURAT-sponsored research team comprising Paul Jennings at the Department of Physiology and Medical Physics, Innsbruck Medical University (Austria), and Alex Seiler and Manfred Watzele at Roche Penzberg (Germany), used continuous real-time impedance measurements with the xCELLigence System to investigate renal epithelial monolayer formation and barrier function. To test repeated dose effects, a human renal proximal tubule cell line (RPTEC/TERT1, Evercyte GmbH Vienna) was cultured on electronic sensor-containing E-Plates 96. Cell impedance was monitored over several weeks in culture, and the effect of nephrotoxin treatment on cell impedance was investigated. Findings showed that the three different nephrotoxins initially increased impedance values as epithelial cell morphology was altered, followed by a decrease in impedance due to cell death.
The xCELLigence System was shown to be a sensitive, non-invasive tool for monitoring repeated dose effects on epithelial cell function and cytotoxicity. Unlike the more laborious transepithelial electrical resistance (TEER) assay, this in vitro assay is a simple, automated, non-invasive, functional readout with very high temporal resolution. Assays such as this will we be beneficial in efforts to replace animal testing for long-term repeat dose regimes.