Development and characterization of a human embryonic stem cell-derived 3D neural tissue model for neurotoxicity testing

Sandström, Jenny (Department of Physiology, University of Lausanne, Lausanne, Switzerland) ; Eggermann, Emmanuel (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Charvet, Igor (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Roux, Adrien (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Toni, Nicolas (Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland) ; Greggio, Chiara (Department of Physiology, University of Lausanne, Lausanne, Switzerland) ; Broyer, Alexandra (Department of Physiology, University of Lausanne, Lausanne, Switzerland) ; Monnet-Tschudi, Florianne (Department of Physiology, University of Lausanne, Lausanne, Switzerland) ; Stoppini, Luc (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland)

Alternative models for more rapid compound safety testing are of increasing demand. With emerging techniques using human pluripotent stem cells, the possibility of generating human in vitro models has gained interest, as factors related to species differences could be potentially eliminated. When studying potential neurotoxic effects of a compound it is of crucial importance to have both neurons and glial cells. We have successfully developed a protocol for generating in vitro 3D human neural tissues, using neural progenitor cells derived from human embryonic stem cells. These 3D neural tissues can be maintained for two months and undergo progressive differentiation. We showed a gradual decreased expression of early neural lineage markers, paralleled by an increase in markers specific for mature neurons, astrocytes and oligodendrocytes. At the end of the two-month culture period the neural tissues not only displayed synapses and immature myelin sheaths around axons, but electrophysiological measurements also showed spontaneous activity. Neurotoxicity testing – comparing non-neurotoxic to known neurotoxic model compounds – showed an expected increase in the marker of astroglial reactivity after exposure to known neurotoxicants methylmercury and trimethyltin. Although further characterization and refinement of the model is required, these results indicate its potential usefulness for in vitro neurotoxicity testing.


Keywords:
Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEPIA - Genève
Institute:
inSTI - Institut des Sciences et Technologies industrielles
Date:
2017-02
Pagination:
12 p.
Published in:
Toxicology in Vitro
Numeration (vol. no.):
2017, vol. 38, pp. 124-135
DOI:
ISSN:
0887-2333
Appears in Collection:

Note: The status of this file is: restricted


 Record created 2020-03-13, last modified 2020-03-27

Fulltext:
Download fulltext
PDF

Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)