Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies.

ALTEX
Markus BrüllMarcel Leist

Abstract

Human cell-based neural organoids are increasingly being used for investigations of neurotoxicity, and to study the pathophysiology of neurodegenerative diseases. Here, we present a fast and robust method to generate 3D cultured human dopaminergic neurons (LUHMES) for toxicity testing and long-term culture. Moreover, a plating step was introduced to allow generation of neurite networks with defined 2D orientation and several mm length, while all cell bodies (somata) remained in a 3D, dome-like structure. These cultures, named here 2.5D (for 2.5 dimensional), offer new approaches to quantify toxicant effects on organoids by standard technology and high throughput. For instance, the system reacted to the parkinsonian model toxicants MPP+, rotenone, MG-132 and the ferroptosis-inducer erastin. Moreover, stable incorporation of human stem cell-derived astrocytes or microglia was possible. Added astrocytes stabilized the post mitotic state of the LUHMES neurons and thereby allowed the formation of a stable micro-physiological system. We observed neuroprotection against the proteasome inhibitor MG-132 and the ferroptosis-inducer erastin by such glia. This exemplifies the crucial protective role of astrocytes in neurodegeneration. The ...Continue Reading

Citations

Oct 1, 2020·International Journal of Molecular Sciences·Georgia KouroupiRebecca Matsas
Jul 11, 2020·International Journal of Molecular Sciences·Simon GutbierChristoph Patsch
Dec 4, 2020·Archives of Toxicology·Dominik LoserUdo Kraushaar

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