Neuronal organoids with astrocytes for toxicological studies
2020
Universität Konstanz, Konstanz, Germany
A fast and robust method to generate 3D cultured human dopaminergic neurons (LUHMES) for toxicity testing and long-term culture is presented. A special plating step allows the generation of neurite networks with defined 2D orientation, while all cell bodies (somata) remain in a 3D, dome-like structure. These cultures, named 2.5 dimensional, offer new approaches to quantify toxic effects on organoids by standard technology and high throughput. For instance, the system reacts 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 is possible. Added astrocytes stabilize the postmitotic state of the LUHMES neurons and thereby allow the formation of a stable microphysiological system. Neuroprotection against the proteasome inhibitor MG-132 and the ferroptosis-inducer erastin by such glia is observed. This exemplifies the crucial protective role of astrocytes in neurodegeneration. The modularity of the system is further employed to incorporate microglia together with astrocytes into the organoids. Such ratio-defined, three cell type-based organoids will allow new approaches to study human pathophysiology and toxicology of the nervous system.
Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies
Marcel Leist
Added on: 07-07-2020
[1] https://www.altex.org/index.php/altex/article/view/1486
