Advances in Cerebral Organoid Systems and their Application in Disease Modeling
Abstract
Processes associated with human brain development and function are exceedingly complex, limiting our capacity to investigate disease status and potential treatment strategies in vitro. Recent advancements in human cerebral organoid systems-which replicate early stage neural tube formation, neuroepithelium differentiation, and whole-brain regional differentiation-have allowed researchers to generate more accurate models of brain development and disease. The generation of region-specific cerebral organoids also allows for the direct investigation of the etiology and pathological processes associated with inherited and acquired brain diseases, drug discovery, and drug toxicity. In this review, we provide an overview of various neural differentiation technologies, as well as a critical analysis of their strengths and limitations. We primarily focus on the generation of three-dimensional brain organoid systems and their application in infectious disease modeling, high-throughput compound screening, and neurodevelopmental disease modeling.
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Human brain organoids can fully replicate human biology and potentially reduce translational barriers from experimental findings to therapeutic applications.
“Meanwhile, being entirely derived from human cells, these organoids can fully replicate human biology and potentially reduce the translational barriers from experimental findings to therapeutic applications (20–22), offering advantages over animal models (23–25).”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [21]
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Blue, R., Miranda, S. P., Gu, B. J., & Chen, H. I. (2020) · Neurosurgery · doi:10.1093/neuros/nyaa171 · Cited by 13 · see citing works
Comparing stem cells, transdifferentiation and brain organoids as tools for psychiatric research
Bellon, A. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02780-8 · Cited by 12 · see citing works
Tian, C., Ao, Z., Cerneckis, J., Cai, H., Chen, L., Niu, H., Takayama, K., Kim, J., Shi, Y., Gu, M., et al. (2025) · Science Advances · doi:10.1126/sciadv.adu2708 · Cited by 9 · see citing works
Kandula, A. K. R., Phamornratanakun, T., Gomez, A. H., El‐Mokahal, M., Ma, Z., Feng, Y., & Yang, H. (2025) · Advanced Intelligent Discovery · doi:10.1002/aidi.202400041 · Cited by 5 · see citing works
Tian, C., Ao, Z., Cerneckis, J., Cai, H., Chen, L., Niu, H., Takayama, K., Kim, J., Shi, Y., Gu, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.16.638539 · Cited by 3 · see citing works
Schultz, E. M., Jones, T. J., Xu, S., Dean, D. D., Zechmann, B., Ronca, S. E., & Barr, K. L. (2021) · Preprints.org · doi:10.20944/preprints202101.0480.v1 · Cited by 2 · see citing works
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Generative AI for Cell Type-Specific Fluorescence Image Generation of hPSC-derived Cardiac OrganoidPreprint
Kandula, A. K. R., Phamornratanakun, T., Gomez, A. H., El‐Mokahal, M., Ma, Z., Feng, Y., & Yang, H. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.15.575724 · Cited by 1 · see citing works
From Zero to Neuro-Reprogramming: Innovations in Translational Neuroregenerative Medicine
Galuta, A., & Tsai, E. C. (2019) · University of Ottawa Journal of Medicine · doi:10.18192/uojm.v9i1.4163
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Deciphering Complexity in Human Brain Organoids via a Novel Hurst Exponent Estimation
Ferraz, M. S. A., Muotri, A. R., & Kihara, A. H. (2025) · Physical Review Letters · doi:10.1103/kl6z-ctdd
- Authors
- Liu, F., Huang, J., Zhang, L., Chen, J., Zeng, Y., Tang, Y., & Liu, Z.
- Affiliations
- Xiangya Hospital Central South University (CN)
- Central South University (CN)
- Corresponding author
- Liu, Zhixiong
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 399
- Pages
- 28-38
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2904322283
- Cited by
- 27
- References
- 76
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 2
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81472693)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- brain organoids, disease modeling, neuronal differentiation, neurulation, neurodevelopmental disorders, epidemic modeling, high-throughput compound screening, drug discovery, drug toxicity, three-dimensional brain model
- MeSH terms
- Animals, Brain, Brain Diseases, Humans, Models, Neurological, Organoids
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