Brain organoids: A revolutionary tool for modeling neurological disorders and development of therapeutics

Biotechnol Bioeng. 2024 Feb;121(2):489-506. doi: 10.1002/bit.28606. Epub 2023 Nov 28.

Abstract

Brain organoids are self-organized, three-dimensional (3D) aggregates derived from pluripotent stem cells that have cell types and cellular architectures resembling those of the developing human brain. The current understanding of human brain developmental processes and neurological disorders has advanced significantly with the introduction of this in vitro model. Brain organoids serve as a translational link between two-dimensional (2D) cultures and in vivo models which imitate the neural tube formation at the early and late stages and the differentiation of neuroepithelium with whole-brain regionalization. In addition, the generation of region-specific brain organoids made it possible to investigate the pathogenic and etiological aspects of acquired and inherited brain disease along with drug discovery and drug toxicity testing. In this review article, we first summarize an overview of the existing methods and platforms used for generating brain organoids and their limitations and then discuss the recent advancement in brain organoid technology. In addition, we discuss how brain organoids have been used to model aspects of neurodevelopmental and neurodegenerative diseases, including autism spectrum disorder (ASD), Rett syndrome, Zika virus-related microcephaly, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).

Keywords: embryoid bodies (EBs); human brain organoids (HBOs); human induced pluripotent stem cells (hiPSCs); neural progenitor cells (NPCs); neurological disorders.

Publication types

  • Review

MeSH terms

  • Autism Spectrum Disorder*
  • Brain
  • Humans
  • Induced Pluripotent Stem Cells*
  • Nervous System Diseases*
  • Organoids
  • Zika Virus Infection*
  • Zika Virus*