Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture

Preynat-Seauve, Olivier (Department of Pathology and Immunology, Faculty of Medicine, University of Geneva and Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland) ; Suter, David M. (Department of Pathology and Immunology, Faculty of Medicine, University of Geneva and Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland) ; Tirefort, Diderik (Department of Pathology and Immunology, Faculty of Medicine, University of Geneva and Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland) ; Turchi, Laurent (INSERM, Faculty of Medicine, Nice, France) ; Virolle, Thierry (INSERM, Faculty of Medicine, Nice, France) ; Chneiweiss, Hervé (INSERM, Faculty of Medicine Paris Descartes, Paris, France) ; Foti, Michelangelo (Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Switzerland) ; Lobrinus, Johannes-Alexander (Neuropathology Unit, Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland) ; Stoppini, Luc (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Feki, Anis (Stem Cell Research Laboratory, Department of Gynecology and Obstetrics, Geneva Hospital, Switzerland) ; Dubois-Dauphin, Michel (Department of Pathology and Immunology, Faculty of Medicine, University of Geneva and Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland) ; Krause, Karl Heinz (Department of Pathology and Immunology, Faculty of Medicine, University of Geneva and Department of Genetic and Laboratory Medicine, Geneva Hospital, Switzerland)

Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air‐liquid interface‐based culture of human ESC. This culture system allows three‐dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3‐month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural‐like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air‐liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural‐like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three‐dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.


Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEPIA - Genève
Institute:
inSTI - Institut des Sciences et Technologies industrielles
Date:
2009-03
Pagination:
12 p.
Published in:
Stem Cells
Numeration (vol. no.):
2009, vol. 27, no. 3, pp. 509-520
DOI:
ISSN:
1066-5099
Appears in Collection:



 Record created 2020-02-21, last modified 2020-02-28

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