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.

Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity / Ciarpella, F.; Zamfir, R. G.; Campanelli, A.; Ren, E.; Pedrotti, G.; Bottani, E.; Borioli, A.; Caron, D.; Di Chio, M.; Dolci, S.; Ahtiainen, A.; Malpeli, G.; Malerba, G.; Bardoni, R.; Fumagalli, G.; Hyttinen, J.; Bifari, F.; Palazzolo, G.; Panuccio, G.; Curia, G.; Decimo, I.. - In: ISCIENCE. - ISSN 2589-0042. - 24:12(2021), pp. 1-36. [10.1016/j.isci.2021.103438]

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

Ren E.;Bardoni R.;Curia G.;
2021

Abstract

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.
2021
24
12
1
36
Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity / Ciarpella, F.; Zamfir, R. G.; Campanelli, A.; Ren, E.; Pedrotti, G.; Bottani, E.; Borioli, A.; Caron, D.; Di Chio, M.; Dolci, S.; Ahtiainen, A.; Malpeli, G.; Malerba, G.; Bardoni, R.; Fumagalli, G.; Hyttinen, J.; Bifari, F.; Palazzolo, G.; Panuccio, G.; Curia, G.; Decimo, I.. - In: ISCIENCE. - ISSN 2589-0042. - 24:12(2021), pp. 1-36. [10.1016/j.isci.2021.103438]
Ciarpella, F.; Zamfir, R. G.; Campanelli, A.; Ren, E.; Pedrotti, G.; Bottani, E.; Borioli, A.; Caron, D.; Di Chio, M.; Dolci, S.; Ahtiainen, A.; Malpeli, G.; Malerba, G.; Bardoni, R.; Fumagalli, G.; Hyttinen, J.; Bifari, F.; Palazzolo, G.; Panuccio, G.; Curia, G.; Decimo, I.
File in questo prodotto:
File Dimensione Formato  
ciarpella_2021.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 11.26 MB
Formato Adobe PDF
11.26 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1257278
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact