Comparative human and rat neurospheres reveal species differences in chemical effects on neurodevelopmental key events
Abstract
The developing brain is highly vulnerable to the adverse effects of chemicals, resulting in neurodevelopmental disorders in humans. Currently, animal experiments in the rat are the gold standard for developmental neurotoxicity (DNT) testing; however, these guideline studies are insufficient in terms of animal use, time and costs and bear the issue of species extrapolation. Therefore, the necessity for alternative methods that predict DNT of chemicals faster, cheaper and with a high predictivity for humans is internationally agreed on. In this respect, we developed an in vitro model for DNT key event screening, which is based on primary human and rat neural progenitor cells grown as neurospheres. They are able to mimic basic processes of early fetal brain development and enable an investigation of species differences between humans and rodents in corresponding cellular models. The goal of this study was to investigate to what extent human and rat neurospheres were able to correctly predict the DNT potential of a well-characterized training set of nine chemicals by investigating effects on progenitor cell proliferation, migration and neuronal differentiation in parallel to cell viability, and to compare these chemical responses between human and rat neurospheres. We demonstrate that (1) by correlating these human and rat in vitro results to existing in vivo data, human and rat neurospheres classified most compounds correctly and thus may serve as a valuable component of a modul…
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Human and rat neural progenitor cell spheroids both correctly classified nine test chemicals for DNT potential but differed in sensitivity profiles.
“Similarly, Baumann et al. (2016) found that while both human and rat neural progenitor cell spheroids correctly classified nine test chemicals for DNT potential, they differed in sensitivity profiles, underscoring the importance of human-based models for accurate hazard assessment.”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Baumann et al. (2016)
Cites
MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates
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Blum, J., Masjosthusmann, S., Bartmann, K., Bendt, F., Dolde, X., Dönmez, A., Förster, N., Holzer, A.-K., Hübenthal, U., Keßel, H. E., et al. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2022.137035 · Cited by 105 · see citing works
Self-citationHarrill, J. A., Freudenrich, T., Wallace, K., Ball, K., Shafer, T. J., & Mundy, W. R. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.04.001 · Cited by 86 · see citing works
Sachana, M., Shafer, T. J., & Terron, A. (2021) · Biology · doi:10.3390/biology10020086 · Cited by 71 · see citing works
Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation
Koch, K., Bartmann, K., Hartmann, J., Kapr, J., Klose, J., Kuchovská, E., Pahl, M., Schlüppmann, K., Zühr, E., & Fritsche, E. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.816370 · Cited by 48 · see citing works
Self-citationSpänle, J. V., Haiber, L. M., & Seeger, B. (2026) · Frontiers in Toxicology · doi:10.3389/ftox.2026.1800157 · Cited by 1 · see citing works
- Authors
- Baumann, J., Gassmann, K., Masjosthusmann, S., DeBoer, D., Bendt, F., Giersiefer, S., & Fritsche, E.
- Venue
- Archives of Toxicology
- Published
- 2015-07-28
- Volume
- 90
- Issue
- 6
- Pages
- 1415-1427
- ISSN
- 0340-5761
- 1432-0738
- Cited by
- 74
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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