Modeling Neurological Disorders in 3D Organoids Using Human-Derived Pluripotent Stem Cells

Modeling neurological disorders is challenging because they often have both endogenous and exogenous causes. Brain organoids consist of three-dimensional (3D) self-organizing brain tissue which increasingly is being used to model various aspects of brain development and disorders, such as the generation of neurons, neuronal migration, and functional networks. These organoids have been recognized as important in vitro tools to model developmental features of the brain, including neurological disorders, which can provide insights into the molecular mechanisms involved in those disorders. In this review, we describe recent advances in the generation of two-dimensional (2D), 3D, and blood-brain barrier models that were derived from induced pluripotent stem cells (iPSCs) and we discuss their advantages and limitations in modeling diseases, as well as explore the development of a vascularized and functional 3D model of brain processes. This review also examines the applications of brain organoids for modeling major neurodegenerative diseases and neurodevelopmental disorders.

Automated summary

Brain organoids are important in vitro tools for modeling various aspects of brain development and disorders, providing insights into the molecular mechanisms involved in neurological diseases. Models derived from induced pluripotent stem cells (iPSCs), including 2D, 3D, and blood-brain barrier models, have advantages in disease modeling and can be used to develop vascularized and functional 3D models of brain processes. The applications of brain organoids for modeling major neurodegenerative diseases and neurodevelopmental disorders are also explored in this review.