Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity
Francesca Ciarpella,
Raluca Georgiana Zamfir,
Alessandra Campanelli,
Elisa Ren,
Giulia Pedrotti,
Emanuela Bottani,
Andrea Borioli,
Davide Caron,
Marzia Di Chio,
Sissi Dolci,
Annika Ahtiainen,
Giorgio Malpeli,
Giovanni Malerba,
Rita Bardoni,
Guido Fumagalli,
Jari Hyttinen,
Francesco Bifari,
Gemma Palazzolo,
Gabriella Panuccio,
Giulia Curia,
Ilaria Decimo
Affiliations
Francesca Ciarpella
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Raluca Georgiana Zamfir
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Alessandra Campanelli
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Elisa Ren
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Giulia Pedrotti
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Emanuela Bottani
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Andrea Borioli
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Davide Caron
Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy
Marzia Di Chio
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Sissi Dolci
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Annika Ahtiainen
BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
Giorgio Malpeli
Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy
Giovanni Malerba
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy
Rita Bardoni
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Guido Fumagalli
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy
Jari Hyttinen
BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
Francesco Bifari
Laboratory of Cell Metabolism and Regenerative Medicine, Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy
Gemma Palazzolo
Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy
Gabriella Panuccio
Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Genova, Italy
Giulia Curia
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Ilaria Decimo
Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, P.le Scuro 10, 37134 Verona, Italy; Corresponding author
Summary: 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.
