An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_FEAAC77037C3
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat.
Journal
Toxicology in vitro
Author(s)
Nunes C., Singh P., Mazidi Z., Murphy C., Bourguignon A., Wellens S., Chandrasekaran V., Ghosh S., Zana M., Pamies D., Thomas A., Verfaillie C., Culot M., Dinnyes A., Hardy B., Wilmes A., Jennings P., Grillari R., Grillari J., Zurich M.G., Exner T.
ISSN
1879-3177 (Electronic)
ISSN-L
0887-2333
Publication state
Published
Issued date
06/2022
Peer-reviewed
Oui
Volume
81
Pages
105333
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Most OECD guidelines for chemical risk assessment include tests performed on animals, raising financial, ethical and scientific concerns. Thus, the development of human-based models for toxicity testing is highly encouraged. Here, we propose an in vitro multi-organ strategy to assess the toxicity of chemicals. Human induced pluripotent stem cells (hiPSCs)-derived models of the brain, blood-brain barrier, kidney, liver and vasculature were generated and exposed to paraquat (PQ), a widely employed herbicide with known toxic effects in kidneys and brain. The models showed differential cytotoxic sensitivity to PQ after acute exposure. TempO-Seq analysis with a set of 3565 probes revealed the deregulation of oxidative stress, unfolded protein response and estrogen receptor-mediated signaling pathways, in line with the existing knowledge on PQ mechanisms of action. The main advantages of this strategy are to assess chemical toxicity on multiple tissues/organs in parallel, exclusively in human cells, eliminating the interspecies bias, allowing a better evaluation of the differential sensitivity of the models representing the diverse organs, and increasing the chance to identify toxic compounds. Furthermore, although we focused on the mechanisms of action of PQ shared by the different models, this strategy would also allow for organ-specific toxicity testing, by including more cell type-specific probes for TempO-Seq analyses. In conclusion, we believe this strategy will participate in the further improvement of chemical risk assessment for human health.
Keywords
Animals, Herbicides/metabolism, Herbicides/toxicity, Humans, Induced Pluripotent Stem Cells, Liver/metabolism, Oxidative Stress, Paraquat/toxicity, Acute toxicity, Human induced pluripotent stem cells, New approach methodology, Paraquat, Toxicology
Pubmed
Web of science
Open Access
Yes
Create date
21/02/2022 9:43
Last modification date
27/08/2022 6:40
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