The Emerging New Modeling Technique of Cerebral Organoids

 

The use of cerebral organoids is a relatively new field of 3D modeling in the last decade. Made up from pluripotent stem cells, these cells grow into cerebral tissue like that of the mammal brain. It is being widely used, and is still developing as a tool to study prenatal neurodevelopment, drug pathology, and genetic precursors

In the article, “Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles” Logan et al. examined the growth of these cerebral organoids and focused on electrophysiological developments comparatively to fetal and adult brain tissue for the first time. Growing iPSCs for a 2 month differentiation period into embryoids, epithelial tissue then cerebral organoids. The researchers were able to find electrical activity within these organoids like human brain tissue through ion channel responses with drug (profonol) and action potentials of neurons. In this, they were able to find genetic markers for brain cells such as neurons. Their findings showed in overlap between fetal brain tissue and cerebral organoids in neural signaling pathways. As well as gave more analysis for which to further develop modeling in the adult brain for neurotransmitter and functional responses within drug pathways. What makes this study most unique is its groundwork focus on the cerebral organoids as a model and testing the limits to which it can be used for future analysis.

In the previous article their goal was to use cerebral organoids as a tool for further comparisons between adult and fetal brain tissue. Similarly, researchers at North Carolina State University used the same techniques of cerebral organoids to study the genetic precursor of Angelman syndrome.  Angelman’s syndrome is a disorder of neurodevelopment that can cause delays in development, speech impairment, ataxia, and behavioral traits like overexcitability. With no cure yet to be found, it effects about 1 in 15,000 people and people diagnosed can expect a normal life expectancy with care. Here in this experiment, the use of cerebral organoids was fundamental in their approach to study prenatal neurodevelopment in humans, that could not be replicated within mice. In this study, the researchers focused on UBE3A protein for its role in early neurodevelopment in which low levels of activity can cause Angelman syndrome. Researchers were able to use cerebral organoids due to being like the first trimesters of fetuses, and thus an accurate model for neurodevelopment and disease etiology especially in the functionality of UBE3A.

Both studies had the requirement of cerebral organoids in modeling neuronal development and were able to discover great conclusions as a result of this cutting-edge modeling. These studies help lay further evidence for a shift in modeling of the brain not so readily available before, as well as future applications to study the adult brain in development, drug pathology or disease analysis. Hopefully, further research will continue to take this new model and open up pathways for further study on the human brain

 

 

 

Logan, S., Arzua, T., Yan, Y., Jiang, C., Liu, X., Yu, L., . . . Bai, X. (2020). Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles. Cells, 9(5), 1301. doi:10.3390/cells9051301

Sen, D., Voulgaropoulos, A., Drobna, Z., & Keung, A. J. (2020). Human Cerebral Organoids Reveal Early Spatiotemporal Dynamics and Pharmacological Responses of UBE3A. Stem Cell Reports. doi:10.1016/j.stemcr.2020.08.006