Your browser doesn't support javascript.
loading
An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat.
Nunes, Carolina; Singh, Pranika; Mazidi, Zahra; Murphy, Cormac; Bourguignon, Aurore; Wellens, Sara; Chandrasekaran, Vidya; Ghosh, Sreya; Zana, Melinda; Pamies, David; Thomas, Aurélien; Verfaillie, Catherine; Culot, Maxime; Dinnyes, Andras; Hardy, Barry; Wilmes, Anja; Jennings, Paul; Grillari, Regina; Grillari, Johannes; Zurich, Marie-Gabrielle; Exner, Thomas.
Afiliación
  • Nunes C; Department of Biomedical Sciences, University of Lausanne, Rue du Bugnon 7, 1005 Lausanne, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Missionsstrasse 64, 4055 Basel, Switzerland.
  • Singh P; Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057 Basel, Switzerland; Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
  • Mazidi Z; Evercyte GmbH, Vienna, Austria; Institute of Molecular Biotechnology, Department of Biotechnology, BOKU - University of Natural Resource and Life science (BOKU), Vienna, Austria.
  • Murphy C; Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, the Netherlands.
  • Bourguignon A; BioTalentum Ltd, Gödöllo, Hungary; Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Gödöllö, Hungary.
  • Wellens S; University of Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des sciences Jean Perrin, Rue Jean Souvraz SP18, F-62300 Lens, France.
  • Chandrasekaran V; Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, the Netherlands.
  • Ghosh S; Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium.
  • Zana M; BioTalentum Ltd, Gödöllo, Hungary.
  • Pamies D; Department of Biomedical Sciences, University of Lausanne, Rue du Bugnon 7, 1005 Lausanne, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Missionsstrasse 64, 4055 Basel, Switzerland.
  • Thomas A; Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Geneva, Switzerland; Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
  • Verfaillie C; Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium.
  • Culot M; University of Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des sciences Jean Perrin, Rue Jean Souvraz SP18, F-62300 Lens, France.
  • Dinnyes A; BioTalentum Ltd, Gödöllo, Hungary; Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Gödöllö, Hungary; Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary.
  • Hardy B; Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057 Basel, Switzerland.
  • Wilmes A; Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, the Netherlands.
  • Jennings P; Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, the Netherlands.
  • Grillari R; Evercyte GmbH, Vienna, Austria.
  • Grillari J; Evercyte GmbH, Vienna, Austria; Institute of Molecular Biotechnology, Department of Biotechnology, BOKU - University of Natural Resource and Life science (BOKU), Vienna, Austria; Ludwig Boltzmann Institute for Traumatology Research Center in cooperation with AUVA, Vienna, Austria.
  • Zurich MG; Department of Biomedical Sciences, University of Lausanne, Rue du Bugnon 7, 1005 Lausanne, Switzerland; Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Missionsstrasse 64, 4055 Basel, Switzerland. Electronic address: mzurich@unil.ch.
  • Exner T; Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057 Basel, Switzerland; Seven Past Nine d.o.o., Hribljane 10, 1380 Cerknica, Slovenia. Electronic address: thomas.exner@sevenpastnine.com.
Toxicol In Vitro ; 81: 105333, 2022 Jun.
Article en En | MEDLINE | ID: mdl-35182771
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.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Herbicidas Tipo de estudio: Risk_factors_studies Aspecto: Ethics Límite: Animals / Humans Idioma: En Revista: Toxicol In Vitro Asunto de la revista: TOXICOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Pluripotentes Inducidas / Herbicidas Tipo de estudio: Risk_factors_studies Aspecto: Ethics Límite: Animals / Humans Idioma: En Revista: Toxicol In Vitro Asunto de la revista: TOXICOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Suiza
...