Recapitulation and investigation of human brain development with neural organoids

Abstract

Organoids are 3D cultured tissues derived from stem cells that resemble the structure of living organs. Based on the accumulated knowledge of neural development, neural organoids that recapitulate neural tissue have been created by inducing self-organized neural differentiation of stem cells. Neural organoid techniques have been applied to human pluripotent stem cells to differentiate 3D human neural tissues in culture. Various methods have been developed to generate neural tissues of different regions. Currently, neural organoid technology has several significant limitations, which are being overcome in an attempt to create neural organoids that more faithfully recapitulate the living brain. The rapidly advancing neural organoid technology enables the use of living human neural tissue as research material and contributes to our understanding of the development, structure and function of the human nervous system, and is expected to be used to overcome neurological diseases and for regenerative medicine.

Keywords: 3D culture; Human brain development; Neural induction; Neural organoid; Pluripotent stem cells; Regional patterning; Self-organization.

Fig. 1

Emergence and innovation of neural organoid protocols. Chronology of the emergence of key methods related to neural organoid differentiation. Blue, yellow, magenta and green colors indicate differentiation protocols for human neural cells, 3D neural organoids, nonneuronal cells and advanced protocols, respectively.

Fig. 2

Basic protocols for neural organoids. Timeline of the three fundamental protocols for differentiation of neural organoids from human PSCs.