The human brain is a highly complex organ comprised of a variety of cell types and that are largely generated during embryonic development. While this process is invariable in vivo, it is unclear if this can be recapitulated outside of the embryo. Investigation of neurodevelopment and neurological disease is difficult due to the lack of reliable in vitro models that can capture the complexity of the brain. Organoids have recently become highly pursued due to their 3D nature, cellular diversity, and cell-cell interactions, which are not available when cultured as a traditional 2D monolayer. Despite the successful generation of human brain organoids and spheroids using pluripotent stem cells with diverse cell types characteristic of defined brain regions including the cerebral cortex, these models are incredibly inconsistent and not reproducible.

Technology: Dr. Arlotta’s lab has developed four distinct protocols for producing 3D brain organoids and spheroids in a developmentally constrained manner that overcomes organoid variations from individual to experimental batch and genetic background and sex. In addition, these organoids can be cultured long term and are highly reproducible. The brain organoids have extensive cellular diversity of a complex central nervous system (CNS) region that can be consistently generated outside of an embryo. Implementing the use of the brain organoids enables the investigation of human brain development and neurodevelopmental disorders.

Advantages: Establishing a reproducible in vitro brain model allows for investigation of developmental abnormalities associated with human neurological disease that has not been accessible in the past. Brain organoids enable a platform for improved understanding of neuropsychiatric diseases, neurodevelopmental disorders, neurological diseases, and drug efficacy. Long-term and reproducible cultures of brain organoids could enable engineering disease models of specific mutations or making patient-derived organoids.