Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology

Archives of Toxicology, vol. 99, pp. 1271–1285

Abstract

Imaging technologies are being increasingly used in biomedical research and experimental toxicology to gather morphological and functional information from cellular models. There is a concrete opportunity of incorporating imaging-based in vitro methods in international guidelines to respond to regulatory requirements with human relevant data. To translate these methods from R&D to international regulatory acceptance, the community needs to implement test methods under quality management systems, assess inter-laboratory transferability, and demonstrate data reliability and robustness. This article summarises current challenges associated with image acquisition, image analysis, including artificial intelligence, and data management of imaging-based methods, with examples from the developmental neurotoxicity in vitro battery and phenotypic profiling assays. The article includes considerations on specific needs and potential solutions to design and implement future validation and transferability studies.

Authors 22

1. Monica Piergiovanni corresponding

   European Commission · Joint Research Centre

   Affiliation as printed

   European Commission, Joint Research Centre (JRC), Ispra, Italy. monica.piergiovanni@ec.europa.eu

   European Commission, Joint Research Centre (JRC), Ispra, Italy

2. Milena Mennecozzi

   Joint Research Centre

   Affiliation as printed

   European Commission, Joint Research Centre (JRC), Ispra, Italy

3. Erio Barale-Thomas

   Janssen (Belgium)

   Affiliation as printed

   Preclinical Sciences and Translational Safety, Janssen Pharmaceuticals, Beerse, Belgium

4. Davide Danovi

   King's College London

   Affiliation as printed

   Department of Basic and Clinical Neuroscience, King's College London, London, UK

5. Sebastian Dunst

   Federal Institute for Risk Assessment

   Affiliation as printed

   German Centre for the Protection of Laboratory Animals (Bf3R), Department Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment, Berlin, Germany

6. David Egan
   Affiliation as printed

   Core Life Analytics BV, 57 Kabelweg, 1014 BA, Amsterdam, The Netherlands

7. Aurora Fassi

   Joint Research Centre

   Affiliation as printed

   European Commission, Joint Research Centre (JRC), Ispra, Italy

8. Matthew Hartley

   European Bioinformatics Institute

   Affiliation as printed

   European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK

9. Philipp Kainz
   Affiliation as printed

   KOLAIDO GmbH, Altenrhein, Switzerland

10. Katharina Koch

    Leibniz Institute of Environmental Medicine

    Affiliation as printed

    DNTOX GmbH, Duesseldorf, Germany

    IUF - Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany

    IUF – Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany

11. Sylvia E. Le Dévédec Aachen Leiden Academic Centre for Drug Research Faculty of Science, Leiden University

    Leiden University

    Affiliation as printed

    Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University, 2333, Leiden, Netherlands

12. Iris Mangas

    European Food Safety Authority

    Affiliation as printed

    European Food Safety Authority (EFSA), Parma, Italy

13. Johanna Nyffeler

    Helmholtz Centre for Environmental Research

    Affiliation as printed

    Department of Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany

    Department of Ecotoxicology, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany

14. Enrico A. Pesenti
    Affiliation as printed

    Crown Bioscience Inc, 16550 West Bernardo Drive, Building 5, Suite 525, San Diego, CA, 92127, USA

15. Fernanda Ricci

    Axxam (Italy)

    Affiliation as printed

    Axxam SpA, Bresso, Italy

16. Christopher Schmied

    EU-OPENSCREEN

    Affiliation as printed

    EU-OPENSCREEN ERIC, Campus Berlin-Buch, Robert-Roessle-Str. 10, 13125, Berlin, Germany

17. Alexander Schreiner

    Revvity (United States)

    Affiliation as printed

    Revvity Health Sciences, Inc, Waltham, MA, USA

18. Nadine Stokar‐Regenscheit

    Roche (Switzerland)

    Affiliation as printed

    Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland

    Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland

19. Jason R. Swedlow

    University of Dundee · National Phenotypic Screening Centre

    Affiliation as printed

    Divisions of Computational Biology and Molecular, Cell and Developmental Biology, School of Life Sciences, National Phenotypic Screening Centre, University of Dundee, Dundee, UK

20. Virginie Uhlmann

    University of Zurich

    Affiliation as printed

    BioVisionCenter, University of Zürich, Zurich, Switzerland

21. Fredrik C. Wieland
    Affiliation as printed

    Life Science Business Europe, Yokogawa Deutschland GmbH, Ratingen, Germany

22. Maurice P. Whelan

    Joint Research Centre

    Affiliation as printed

    European Commission, Joint Research Centre (JRC), Ispra, Italy