Abstract
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.
Highlights
Neurons and glial cells are major cellular types of the central nervous system, which are essential for normal brain function and are implicated in most neurological disorders
Transcriptome analysis revealed that microglia-related genes are expressed differently in microglia-like cells (MG) when they are co-cultured with neural organoids (Song et al, 2019b). These findings indicate that generating microglial from induced pluripotent stem cells (iPSCs) is a significant advance in iPSC technology, whereby non-neuronal cells can be readily derived from iPSCs, providing an avenue for more efficient designs of organoid models in the future
Conforti et al (2018) produced a 3D cortical organoid using humanderived induced pluripotent stem cells (hiPSCs) derived from Huntington’s disease (HD) patients, which was characterized by developmental defects in ventral-telencephalic and striatal formation during maturation
Summary
Neurons and glial cells (astrocytes, oligodendrocytes, and microglia) are major cellular types of the central nervous system, which are essential for normal brain function and are implicated in most neurological disorders. The 3D brain organoid consists of various cell types that can recapitulate cortical neuronal layers, cellular compartmentalization, and brain-like functions Such organoids can recapitulate the development of embryonic tissue more accurately than that of the 2D culture of hiPSCs. 3D organoids have more promise for the investigation of human brain development and complex human diseases, including neurodevelopmental and neurodegenerative disorders. We first present different 2D culture methods that are used to generate various neuronal and non-neuronal cells derived from hiPSCs. we discuss the organoid technologies that use iPSCs as in vitro models of neurological disorders. The dual-SMAD inhibition method is a procedure that inhibits SMAD-dependent transforming growth factor-beta (TGFβ) and BMP signaling pathways with SB431542 and noggin This efficiently converts hiPSCs to NSCs, which are characterized by specific markers (Table 1). Because the ability to induce several types of neurons in culture is critically important for receiving, processing, and transmitting the information through their self-created networks and because neurodegenerative diseases may affect many of these neuronal connections, the production of different subtypes of neurons
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