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Human brain organoids produce anatomically relevant cellular structures and recapitulate key aspects of brain function, which holds great potential to model neurological diseases and screen therapeutics. However, the long growth time of 3D systems complicates the culturing of brain organoids and results in heterogeneity across samples hampering their applications. We developed an integrated platform to enable robust and long-term culturing of 3D brain organoids. We designed a mesofluidic bioreactor device based on a reaction-diffusion scaling theory, which achieves robust media exchange for sufficient nutrient delivery in long-term culture. We integrated this device with longitudinal tracking and machine learning-based classification tools to enable non-invasive quality control of live organoids. This integrated platform allows for sample pre-selection for downstream molecular analysis. Transcriptome analyses of organoids revealed that our mesofluidic bioreactor promoted organoid development while reducing cell death. Our platform thus offers a generalizable tool to establish reproducible culture standards for 3D cellular systems for a variety of applications beyond brain organoids.
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http://dx.doi.org/10.1002/admt.202400473 | DOI Listing |
EMBO 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.
View Article and Find Full Text PDFBrain
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.