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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).
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http://dx.doi.org/10.1002/bit.28606 | DOI Listing |
Brain
September 2025
Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan.
Animal models of the pathology of Parkinson's disease (PD) have provided most of the treatments to date, but the disease is restricted to human patients. In vitro models using human pluripotent stem cells (hPSCs)-derived neural organoids have provided improved access to study PD etiology. This study established a method to generate human striatal-midbrain assembloids (hSMAs) from hPSCs for modeling alpha-synuclein (α-syn) propagation and recapitulating basal ganglia circuits, including nigrostriatal and striatonigral pathways.
View Article and Find Full Text PDFiScience
September 2025
Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Hessen, Germany.
Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing , a common oncogene in brain tumors. GFP/c-MYC cells were isolated from tumor organoids and used in two different approaches: GFP/c-MYC cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids.
View Article and Find Full Text PDFPhytomedicine
August 2025
Laboratory of Neurological Disease Modeling and Translational Research, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
Background: Stress is a prevalent mental health concern that often emerges in late adolescence or early adulthood. Since 2007, the Food and Drug Administration (FDA) has not approved any novel anxiolytic pharmaceuticals, leading to increased interest in nutritional supplements as alternative therapies for stress management.
Purpose: Building on our previous study, this work aims to investigate the synergistic effects of Theanine (Th) and Walnut Peptide (WP) on stress mitigation and cognitive enhancement.
Cell Regen
September 2025
Center for Translational Neural Regeneration Research, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
Neural regeneration stands at the forefront of neuroscience, aiming to repair and restore function to damaged neural tissues, particularly within the central nervous system (CNS), where regenerative capacity is inherently limited. However, recent breakthroughs in biotechnology, especially the revolutions in genetic engineering, materials science, multi-omics, and imaging, have promoted the development of neural regeneration. This review highlights the latest cutting-edge technologies driving progress in the field, including optogenetics, chemogenetics, three-dimensional (3D) culture models, gene editing, single-cell sequencing, and 3D imaging.
View Article and Find Full Text PDFGut Liver
September 2025
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Background/aims: Patient-derived organoids (PDOs) are promising preclinical models that replicate critical tumor features. However, intratumoral heterogeneity challenges the clinical utility of PDOs, especially in capturing diverse tumor cell subpopulations.
Methods: Single-cell transcriptomics was used to analyze PDOs from distinct sites within a single gastric cancer tumor, aiming to assess their ability to reflect intratumoral heterogeneity.