title: Evaluation of impedance-based label-free technology as a tool for pharmacology and toxicology investigations.
abstract: The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objective of the present study was to further assess the usefulness of the real-time cell analyzer (RTCA) and, in particular, the xCELLigence platform, in the context of early drug development for pharmacology and toxicology investigations. In the present manuscript, four cellular models were exposed to 50 compounds to compare the cell index generated by RTCA and cell viability measured with a traditional viability assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were generated when HepG2 and HepaRG cells were exposed to calcium modulators, antimitotics, DNA damaging and nuclear receptor agents, with a percentage of prediction close to 80% for both cellular models. In a subsequent experiment, HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or not. Based on the DNA damaging signatures, the RTCA technology allowed the detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the non-genotoxic compounds (n = 52). Overall, despite some limitations, the xCELLigence platform is a powerful and reliable tool that can be used in drug discovery for toxicity and pharmacology studies.
authors.affiliation: UCB Pharma SA, Non Clinical Development, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium; E-Mails: helga.gerets@ucb.com (H.G.); karen.tilmant@ucb.com (K.T.); gaelle.toussaint@ucb.com (G.T.); stephane.dhalluin@ucb.com (S.D.).
authors.forename: Franck André
authors.initials: FA
authors.lastname: Atienzar
authors.affiliation: UCB Pharma SA, Non Clinical Development, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium; E-Mails: helga.gerets@ucb.com (H.G.); karen.tilmant@ucb.com (K.T.); gaelle.toussaint@ucb.com (G.T.); stephane.dhalluin@ucb.com (S.D.).
authors.forename: Helga
authors.initials: H
authors.lastname: Gerets
authors.affiliation: UCB Pharma SA, Non Clinical Development, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium; E-Mails: helga.gerets@ucb.com (H.G.); karen.tilmant@ucb.com (K.T.); gaelle.toussaint@ucb.com (G.T.); stephane.dhalluin@ucb.com (S.D.).
authors.forename: Karen
authors.initials: K
authors.lastname: Tilmant
authors.affiliation: UCB Pharma SA, Non Clinical Development, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium; E-Mails: helga.gerets@ucb.com (H.G.); karen.tilmant@ucb.com (K.T.); gaelle.toussaint@ucb.com (G.T.); stephane.dhalluin@ucb.com (S.D.).
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Toussaint
authors.affiliation: UCB Pharma SA, Non Clinical Development, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium; E-Mails: helga.gerets@ucb.com (H.G.); karen.tilmant@ucb.com (K.T.); gaelle.toussaint@ucb.com (G.T.); stephane.dhalluin@ucb.com (S.D.).
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dhalluin
keywords: drug discovery; impedance; investigative pharmacology; predictive toxicology; real-time cell analyzer (RTCA); screening