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

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).

Advancing Endocrine Disruptors via In Vitro Evaluation: Recognizing the Significance of the Organization for Economic Co-Operation and Development and United States Environmental Protection Agency Guidelines, Embracing New Assessment Methods, and the Urgent Need for a Comprehensive Battery of Tests

“…Research based on data from birth cohorts has revealed that when individuals are exposed to endocrine disruptors during crucial stages of neurodevelopment, it can have detrimental effects on various cognitive functions, such as memory and language, as well as attention, emotions, and social behaviors [ 80 , 81 ]. Immortalized human neural progenitor cells (hNPCs) cultivated as three-dimensional floating spheres can represent processes of brain development [ 82 , 83 ]. After exposition to potential endocrine disruptors, the process of NPC proliferation can be studied [ 84 , 85 ].…”

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

“…Other important experimental models for the ZIKV-AD hypothesis would be human-induced pluripotent stem cell (hiPSC)-derived three-dimensional (3D) cultures like brain organoids and spherical self-organized aggregates or hiPSC-derived neurological/immunoregulatory cells [ 92 ]. These models have been widely used for drug repurposing.…”

Human Brain Organoids in the Preclinical Phase of Drug Development for Migraine

“…Organoid models of various neurodegenerative and neurodevelopmental disorders 72 , including Alzheimer's disease, Parkinson's disease, and autistic spectrum disorders, also present opportunities for drug testing. Advancements in generating CNS barrier-forming organoids (CBFOs) contribute to drug permeability testing for CNS drug development.…”