Stem cell-derived systems in toxicology assessment

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Authors
Alves, Paula M.
Blaauboer, Bas J.
Author (Corporation)
Publication date
07/2015
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Type
01A - Journal article
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Parent work
Stem Cells and Development
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DOI of the original publication
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Volume
24
Issue / Number
11
Pages / Duration
1284-96
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Publisher / Publishing institution
Mary Ann Liebert
Place of publication / Event location
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Abstract
Industrial sectors perform toxicological assessments of their potential products to ensure human safety and to fulfill regulatory requirements. These assessments often involve animal testing, but ethical, cost, and time concerns, together with a ban on it in specific sectors, make appropriate in vitro systems indispensable in toxicology. In this study, we summarize the outcome of an EPAA (European Partnership of Alternatives to Animal Testing)-organized workshop on the use of stem cell-derived (SCD) systems in toxicology, with a focus on industrial applications. SCD systems, in particular, induced pluripotent stem cell-derived, provide physiological cell culture systems of easy access and amenable to a variety of assays. They also present the opportunity to apply the vast repository of existing nonclinical data for the understanding of in vitro to in vivo translation. SCD systems from several toxicologically relevant tissues exist; they generally recapitulate many aspects of physiology and respond to toxicological and pharmacological interventions. However, focused research is necessary to accelerate implementation of SCD systems in an industrial setting and subsequent use of such systems by regulatory authorities. Research is required into the phenotypic characterization of the systems, since methods and protocols for generating terminally differentiated SCD cells are still lacking. Organotypical 3D culture systems in bioreactors and microscale tissue engineering technologies should be fostered, as they promote and maintain differentiation and support coculture systems. They need further development and validation for their successful implementation in toxicity testing in industry. Analytical measures also need to be implemented to enable compound exposure and metabolism measurements for in vitro to in vivo extrapolation. The future of SCD toxicological tests will combine advanced cell culture technologies and biokinetic measurements to support regulatory and research applications. However, scientific and technical hurdles must be overcome before SCD in vitro methods undergo appropriate validation and become accepted in the regulatory arena.
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ISBN
ISSN
1557-8534
1547-3287
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Unpublished
Review
Peer review of the complete publication
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License
Citation
Suter-Dick, L., Alves, P. M., & Blaauboer, B. J. (2015). Stem cell-derived systems in toxicology assessment. Stem Cells and Development, 24(11), 1284–1296. https://doi.org/10.1089/scd.2014.0540