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

Erwin Van Vliet, Mardas Daneshian, Mario Beilmann, Anthony Davies, Eugenio Fava, Roland Fleck, Yvon Julé, Manfred Kansy, Stefan Kustermann, Peter Macko, William R. Mundy, Adrian Roth, Imran Shah, Marianne Uteng, Bob Van De Water, Thomas Hartung, Marcel Leist

Research output: Contribution to journalArticle

Abstract

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. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore, high content imaging is considered a promising technology to address the challenges for the 'Toxicity testing in the 21st century' approach. Currently, high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging academia, pharmaceutical industry and regulatory bodies with the objective to compile the state- of-the-art of the technology in the different institutions. Together they defined technical and methodological gaps, proposed quality control measures and performance standards, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.

Original languageEnglish (US)
Pages (from-to)479-493
Number of pages15
JournalALTEX
Volume31
Issue number4
DOIs
StatePublished - Jan 1 2014

Keywords

  • Drug development
  • High content imaging
  • Mechanistic safety screening
  • Toxicity pathways
  • Toxicology

ASJC Scopus subject areas

  • Pharmacology
  • Medical Laboratory Technology

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  • Cite this

    Van Vliet, E., Daneshian, M., Beilmann, M., Davies, A., Fava, E., Fleck, R., Julé, Y., Kansy, M., Kustermann, S., Macko, P., Mundy, W. R., Roth, A., Shah, I., Uteng, M., Van De Water, B., Hartung, T., & Leist, M. (2014). Current approaches and future role of high content imaging in safety sciences and drug discovery. ALTEX, 31(4), 479-493. https://doi.org/10.14573/altex.1405271