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Neurosci Lett. 2018 Mar 23;670:75-82. doi: 10.1016/j.neulet.2018.01.040. Epub 2018 Feb 20.

Six-month cultured cerebral organoids from human ES cells contain matured neural cells.

Author information

1
Department of Future Basic Medicine, Nara Medical University, Nara, Japan; Department of Neurology, Nara Medical University, Nara, Japan; Department of Molecular Biology, University of Texas Southwestern Medical Center, TX, USA; Department of Neurology, University of Texas Southwestern Medical Center, TX, USA.
2
Department of Future Basic Medicine, Nara Medical University, Nara, Japan.
3
Department of Molecular Biology, University of Texas Southwestern Medical Center, TX, USA; Department of Orthopaedics and Microsurgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
4
Department of Neurology, Nara Medical University, Nara, Japan.
5
Department of Radiation Oncology, Nara Medical University, Nara, Japan.
6
Department of Future Basic Medicine, Nara Medical University, Nara, Japan. Electronic address: nakagawat@naramed-u.ac.jp.
7
Department of Future Basic Medicine, Nara Medical University, Nara, Japan. Electronic address: emori@naramed-u.ac.jp.

Abstract

Recently, researchers have developed protocols for human cerebral organoids using human pluripotent stem cells, which mimic the structure of the developing human brain. Existing research demonstrated that human cerebral organoids which undergo short cultivation periods, contain astrocytes, neurons, and neural stem cells, but lacked mature oligodendrocytes, and mature, fully functional neurons. In this study, we analyzed organoids induced from H9 human embryonic stem (ES) cells that were cultivated for as long as six months. We observed mature oligodendrocytes, positive for MBP (myelin-basic protein), and mature GAD67 (glutamate decarboxylase 67 kDa isoform)-positive inhibitory neurons and VGLUT1 (vesicular glutamate transporter 1)-positive excitatory neurons via immunohistochemical analysis. These observations suggest that long-term cultivation of cerebral organoids can lead to the maturation of human cerebral organoids, which can be used as a tool to study the development of human brains.

KEYWORDS:

Embryonic stem cell; Human cerebral organoid; Matured neural cells; Oligodendrocyte; Pluripotent stem cell

PMID:
29398520
DOI:
10.1016/j.neulet.2018.01.040
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