Brain organoid, also known as a cerebral organoid, refers to an artificial miniature organ that resembles the brain in vitro. In general, brain organoids are generated from pluripotent stem cells using a three-dimensional rotational bioreactor. The human brain is an extremely complex system that contains a variety of neuron types. In this case, human brain study, especially neurodegenerative diseases, becomes extremely difficult. Compared with rodent animal models, brain organoids present more advanced cell composition, maturation, and tissue architecture, which are closer to the human brain. In summary, brain organoids play important roles in neurological research and disease modeling.
Before being used as a model to study disease and gene expression, a series of assays are required for evaluation. For example, transcriptome analysis has been used to simulate the pathology of brain organoids. The TUNEL test is an evaluation indicator of apoptosis in brain organoids. Recently, computational methods have also been used to optimize the culture process of brain organoids.
Fig.1 Cerebral organoid at the interface of in vitro and in vivo. (Chiaradia, 2020)
Classification of the Brain Organoid
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Forebrain organoid - It is the largest area of the human brain composed of the thalamus, the hypothalamus, the limbic system, and the cerebral cortex. The forebrain is the important neural structure that relates to speech, cognition, and emotion. It is also implicated in a series of neuropsychiatric conditions such as autism spectrum disorder and epilepsy.
Cerebellar organoid - Located at the lower back of the brain, the cerebellum is an important regulating center of exercise and also plays an important role in maintaining body balance. Some studies showed that the functional defects of different cerebellar neurons may result in cerebellar dysfunction.
Whole-brain organoid - The brain is the most advanced part of the nervous system and consists of the left and right hemispheres. It is the organ of thinking, leading all activities in the body and regulating the balance between the body and the surrounding environment.
Retinal organoid - Derived from human pluripotent stem cells (hPSCs), the retinal organoid is the three-dimensional structure that recapitulates the spatial and temporal differentiation of the retina. It has been served as an effective in vitro model for retinal development.
Human Pluripotent Stem CellsCultivate Embryoid BodiesInduce NeuroectodermGrow in Gel DropletSpin Brain Organoids in BioreactorCompleted Brain Organoid Ready for Various Applications Fig.2 Schematics show the basic steps for the generation of the cerebral organoid.
Applications of Brain Organoid
Cell fate potential
Clonal lineage tracing
Cell replacement therapy
Cell-type specific genome assays
Research on differences between species
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Chiaradia, I.; Lancaster, M. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nature Neuroscience. 2020, 23(12): 1496-1508.