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Brain organoids are self-organized, three-dimensional (3D) aggregates derived from human embryonic stem cells, induced pluripotent stem cells, or primary organs with cell types and cellular architectures resembling those of the developing human brain. Recent studies have shown the use of region-specific brain organoids for modeling various diseases ranging from neurodevelopmental and neurodegenerative diseases to different brain cancers, which have numerous applications in fundamental research and the development of new drugs, personalized treatment, and regenerative medicine. Consequently, the use of brain organoids in drug discovery is complex and challenging and still an emerging area in this field. This review article summarizes the primary stem cells used in brain organoid generation, region-specific brain organoids, and the functional assays used in their characterization. In addition, we discuss the use of brain organoids in modeling neurodevelopmental and neurodegenerative diseases and pediatric brain cancers, as well as the application of organoids, assembloids, and tumoroids in cancer neuroscience. We further explore the recent advances in using brain organoids in high-throughput screening to improve their use for drug discovery.
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http://dx.doi.org/10.3390/cells14110842 | DOI Listing |
Sci Transl Med
September 2025
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are essential for the formation of myelin sheaths and pivotal for maintaining axonal integrity and conduction. Disruption of these cells and the myelin sheaths they produce is a hallmark of demyelinating conditions like multiple sclerosis or those resulting from certain drug side effects, leading to profound neurological impairments. In this study, we created a human brain organoid comprising neurons, astrocytes, and myelinating oligodendrocytes.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
Institute of Cardiovascular Research, Sleep Medical Center, Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, 646000, China.
Rationale: Genome-wide association studies (GWASs) are used to identify genetic variants for association with schizophrenia (SCZ) risk; however, each GWAS can only reveal a small fraction of this association.
Objectives: This study systematically analyzed multiple GWAS data sets to identify gene subnetwork and pathways associated with SCZ.
Methods: We identified gene subnetwork using dmGWAS program by combining SCZ GWASs and a human interaction network, performed gene-set analysis to test the association of gene subnetwork with clinical symptom scores and disease state, meanwhile, conducted spatiotemporal and tissue-specific expression patterns and cell-type-specific analysis of genes in the subnetwork.
Biochem Biophys Rep
December 2025
Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
Brillouin microscopy allows mechanical investigations of biological materials at the subcellular level and can be integrated with Raman spectroscopy for simultaneous chemical mapping, thus enabling a more comprehensive interpretation of biomechanics. The present study investigates different in vitro glioblastoma models using a combination of Brillouin and Raman microspectroscopy. Spheroids of the U87-MG cell line and two patient-derived cell lines as well as patient-derived organoids were used.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, National Stem Cell Translational Resource Center & Ministry of Education Stem Cell Resource Center, Frontier Science Center for Stem Cell Research, School of Li
Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole-exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids.
View Article and Find Full Text PDFCell Rep
September 2025
Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Un
Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions using induced pluripotent stem cell (iPSC)-derived cortical- and hippocampal-ganglionic eminence assembloids to model developmental and epileptic encephalopathy 13, a condition arising from gain-of-function mutations in the SCN8A gene encoding the sodium channel Nav1.
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