Current drug discovery strategies often utilize cell lines and animal models for compound development, drug screening, efficacy testing, and establishing dose-responses. However, such model systems are often limited, particularly for brain disorders and cancers.
Traditional cell culture systems can unintentionally alter physiological properties of cells given the artificial 2D environment, while animal models are very costly and do not fully recapitulate human disorders or diseases, resulting in less efficient and expensive drug discovery. An improved high throughput model system is necessary that maintains fidelity to in vivo human physiological properties yet can be easily manipulated and tested.
Dr. Song and colleagues have established human 3D brain organoid systems that closely resemble human development and have already been applied for modeling several brain disorders. Using a highly optimized protocol consisting of human stem cells, tissues or cancer cells, and miniaturized spinning bioreactors, 3D brain organoids can be synthesized that recapitulate in vivo properties, contain more functional and mature cells, and have increased yield, stability and survivability. These brain organoids have been utilized for understanding the underlying mechanism of the Zika virus, screening neuroprotective compounds, modeling glioblastoma and identifying personalized therapeutics.
The maintenance of cellular, mechanical and topographical cues in the 3D microenvironment enables enhanced in vitro modeling of brain cancer, and neuropsychiatric and neurodegenerative diseases, to improve and accelerate the efficiency, safety, discovery and cost of drug screening for brain cancer and neuropsychiatric and neurodegenerative diseases.
(See image below for reference.) Overview of human 3D brain organoid generation and use in drug screening.
- Using human-derived cells (e.g., human stem cells, tissue, cancer cells)
- 3D brain organoids are developed that recapitulate in vivo physiological properties. Applications for brain organoids include
- evaluating brain development and disease modeling;
- use in cell therapy; and
- high throughput drug screening, where ultimately drug hits and validation will
- lead to the development of novel pharmacotherapies.
- Improves efficiency and reduces costs of modeling brain disorders and cancers.
- Improves testing of personalized therapeutics and drug response.
- Maintains 3D brain-like cytoarchitecture that recapitulates and retains physiological properties compared to 2D cell lines.
- Test beds for drug screening and genomic manipulation
- Modeling and understanding brain disease pathogenesis
Stage of Development:
- Reliable generation using miniaturized spinning bioreactors
- Applied use for Zika virus (mechanism & screening of therapeutic compounds), and glioblastoma (screening personalized therapeutics)
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