Current approaches and future role of high content imaging in safety sciences and drug discovery

Abstract

* a report of t 4 -the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz and Utrecht sponsored by the Doerenkamp-Zbinden Foundation; participants do not represent their institutions and do not necessarily endorse all recommendations made.Disclaimer: This document has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Summary High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems

The need for strategic development of safety sciences

“…CAAT has started a number of collaborative programs to advance safety sciences, which include the Human Toxome Collaboration (see above), the Evidence-based Toxicology Collaboration (see below), the Good Cell Culture Practice Collaboration (Pamies et al, 2017) building on earlier work steered by ECVAM (Coecke et al, 2005), the Good ReadAcross Practice Collaboration (Patlewicz et al, 2014, Ball et al, 2016Zhu et al, 2016), the Refinement Collaboration (Zurlo and Hutchinson, 2014) and others. CAAT's transatlantic think tank for toxicology (t 4 ) has organized more than 30 workshops to advance concepts of toxicology such as integrated testing strategies (Hartung et al, 2013b;Rovida et al, 2015b), epithelial barrier models (Gordon et al, 2015), 3D cell cultures (Alépée et al, 2014), microphysiological systems (Marx et al, 2016), high-content imaging (van Vliet et al, 2014), and has commissioned a number of white papers. (Andersen et al, 2011.…”

Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: Example lists and criteria for their selection and use_suppl

“…Clear quality control procedures would be required for in vitro models to produce results that are comparable across laboratories, and with the ultimate goal to use data for regulatory purposes. To address biological relevance, several different approaches may be combined (Alepee et al, 2014;Hartung et al, 2013;Smirnova et al, 2015;van Vliet et al, 2014). One approach is directly related to the selection of test compounds: the understanding of the response to tool compounds and mechanistically consistent responses to chemically-related compounds would be helpful to evaluate the biological relevance of the test system.…”

E-cigarettes and the need and opportunities for alternatives to animal testing

“…Many of these have been detailed in this series of articles as well as our workshop reports and shall not be reiterated here. The reader is referred to the respective papers for in vivo (Hartung, 2008a(Hartung, , 2013, in vitro (Hartung, 2007(Hartung, , 2013Hartung and Leist, 2008;Leist et al, 2008) and in silico approaches (Hartung and Hoffmann, 2009;Hartung, 2016c), in vitro work for testing cosmetics (Hartung, 2008b), chemicals (Hartung, 2010b), nanomaterials (Hartung, 2010a;Hartung and Sabbioni, 2011), pharmaceuticals (Rovida et al, 2015b) and food (Hartung and Koëter, 2008), organo-typic cultures (Alépée et al, 2014;Andersen et al, 2014;Hartung, 2014;Marx et al, 2016), refinement of animal testing (Zurlo and Hutchinson, 2014), Integrated Testing Strategies (Hartung et al, 2013a;Rovida et al, 2015a), pathways of toxicity (Hartung and McBride, 2011;Kleensang et al, 2014;Tollefsen et al, 2014), omics technologies (Bouhifd et al, 2013(Bouhifd et al, , 2015aRamirez et al, 2013), and high-content imaging (van Vliet et al, 2014). These approaches come with different advantages and disadvantages in general and in particular for testing e-cigarettes (Tab.…”