Human neural organoids for studying brain cancer and neurodegenerative diseases

Cosset, Erika (Laboratory of Tumor Immunology, Translational Research Center in Onco-Hematology, Department of Internal Medicine Specialities, Faculty of Medicine, University of Geneva) ; Locatelli, Manon (Department of pathology and Immunology, University Medical Center, University of Geneva) ; Marteyn, Antoine (Department of pathology and Immunology, University Medical Center, University of Geneva) ; Lescuyer, Pierre (Laboratory of Toxicology and Therapeutic Drug Monitoring, Geneva University Hospitals) ; Dall Antonia, Florence (Laboratory of Toxicology and Therapeutic Drug Monitoring, Geneva University Hospitals) ; Mor, Flavio maurizio (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Preynat-Seauve, Olivier (Laboratory of Experimental cell therapy, department of Diagnostics, Geneva University Hospitals) ; Stoppini, Luc (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Tieng, Vannary (Department of pathology and Immunology, University Medical Center, University of Geneva)

The lack of relevant in vitro neural models is an important obstacle on medical progress for neuropathologies. Establishment of relevant cellular models is crucial both to better understand the pathological mechanisms of these diseases and identify new therapeutic targets and strategies. To be pertinent, an in vitro model must reproduce the pathological features of a human disease. However, in the context of neurodegenerative disease, a relevant in vitro model should provide neural cell replacement as a valuable therapeutic opportunity. Such a model would not only allow screening of therapeutic molecules but also can be used to optimize neural protocol differentiation [for example, in the context of transplantation in Parkinson's disease (PD)]. This study describes two in vitro protocols of 1) human glioblastoma development within a human neural organoids (NO) and 2) neuron dopaminergic (DA) differentiation generating a three-dimensional (3D) organoid. For this purpose, a well-standardized protocol was established that allows the production of size-calibrated neurospheres derived from human embryonic stem cell (hESC) differentiation. The first model can be used to reveal molecular and cellular events occurring during in glioblastoma development within the neural organoid, while the DA organoid not only represents a suitable source of DA neurons for cell therapy in Parkinson's disease but also can be used for drug testing.


Keywords:
Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEPIA - Genève
Institute:
inSTI - Institut des Sciences et Technologies industrielles
Date:
2019-06
Pagination:
8 p.
Published in:
Journal of Visualized Experiments (JOVE)
DOI:
ISSN:
1940-087X
Appears in Collection:



 Record created 2020-01-24, last modified 2020-01-28

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