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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glutamate Decarboxylase / metabolism
  • Human Embryonic Stem Cells / cytology*
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Myelin Basic Protein / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis / physiology*
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • Organoids / cytology*
  • Organoids / metabolism
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Myelin Basic Protein
  • Vesicular Glutamate Transport Protein 1
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1