Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity.

Autor: Ciarpella F; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Zamfir RG; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Campanelli A; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Ren E; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Pedrotti G; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Bottani E; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Borioli A; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Caron D; Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy., Di Chio M; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Dolci S; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Ahtiainen A; BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland., Malpeli G; Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy., Malerba G; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy., Bardoni R; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Fumagalli G; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy., Hyttinen J; BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland., Bifari F; Laboratory of Cell Metabolism and Regenerative Medicine, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy., Palazzolo G; Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy., Panuccio G; Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy., Curia G; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Decimo I; Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy.
Jazyk: angličtina
Zdroj: IScience [iScience] 2021 Nov 15; Vol. 24 (12), pp. 103438. Date of Electronic Publication: 2021 Nov 15 (Print Publication: 2021).
DOI: 10.1016/j.isci.2021.103438
Abstrakt: Brain organoids are in vitro three-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10-20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly standardized, reproducible, and fast (5 weeks) murine brain organoid model starting from embryonic neural stem cells. We obtained brain organoids, which progressively differentiated and self-organized into 3D networks of functional neurons with dorsal forebrain phenotype. Furthermore, by adding the morphogen WNT3a, we generated brain organoids with specific hippocampal region identity. Overall, our results showed the establishment of a fast, robust and reproducible murine 3D in vitro brain model that may represent a useful tool for high-throughput drug screening and disease modeling.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2021 The Author(s).)
Databáze: MEDLINE