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

Brüll, Markus; Spreng, Anna-Sophie; Gutbier, Simon; Loser, Dominik; Krebs, Alice; Reich, Marvin; Kraushaar, Udo; Britschgi, Markus; Patsch, Christoph; Leist, Marcel

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

Dateien

Bruell_2-1dirw4r5uu96f4.pdfGröße: 21.6 MBDownloads: 685

Datum

2020

Autor:innen

Loser, Dominik

Kraushaar, Udo

Britschgi, Markus

Patsch, Christoph

Leist, Marcel

Angaben zur Forschungsförderung

European Union (EU): 825759
European Union (EU): 681002

Projekt

EUToxRisk21
ENDpoiNTs

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Alternatives to Animal Experimentation : ALTEX. Springer Spektrum. 2020, 37(3). ISSN 1868-596X. eISSN 1868-596X. Available under: doi: 10.14573/altex.1911111

Zusammenfassung

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 modularity of the system was 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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

BRÜLL, Markus, Anna-Sophie SPRENG, Simon GUTBIER, Dominik LOSER, Alice KREBS, Marvin REICH, Udo KRAUSHAAR, Markus BRITSCHGI, Christoph PATSCH, Marcel LEIST, 2020. Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies. In: Alternatives to Animal Experimentation : ALTEX. Springer Spektrum. 2020, 37(3). ISSN 1868-596X. eISSN 1868-596X. Available under: doi: 10.14573/altex.1911111

BibTex

@article{Brull2020Incor-49092,
  year={2020},
  doi={10.14573/altex.1911111},
  title={Incorporation of stem cell-derived astrocytes into neuronal organoids to allow neuro-glial interactions in toxicological studies},
  number={3},
  volume={37},
  issn={1868-596X},
  journal={Alternatives to Animal Experimentation : ALTEX},
  author={Brüll, Markus and Spreng, Anna-Sophie and Gutbier, Simon and Loser, Dominik and Krebs, Alice and Reich, Marvin and Kraushaar, Udo and Britschgi, Markus and Patsch, Christoph and Leist, Marcel}
}

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Universitätsbibliographie

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Begutachtet

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