News Release 

'Brain in a dish' models advance studies of neural development and disease

Questions remain about how well brain organoids mirror the complexity of the cortex

Society for Neuroscience

CHICAGO -- Experimental advances using lab-grown brain organoids are helping to clarify how best to use them as a model system to understand human brain development and diseases. The findings were presented at Neuroscience 2019, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Brain organoids are self-organizing, three-dimensional tissues grown from human stem cells guided to become the cell types and structures found in the brain. These "brains in dishes" display many features of the developing human brain, making them a promising model system to study processes of early human brain development. Recent studies have begun to use brain organoids to model interactions between brain regions, circuit formation, and neurodevelopmental diseases, but it remains unclear how well brain organoids mirror the complexity of human brain development.

Today's new findings show that:

  • Brain organoids reproducibly produce the rich diversity of cell types found in the human cerebral cortex, paving the way for modeling aspects of human cortical development and disease that have never been experimentally accessible outside the embryo (Paola Arlotta, the Broad Institute).
  • Brain organoids that model early neural circuit development support a possible imbalance between excitation and inhibition in the brain as an underlying basis for autism (Michael Nestor, Hussman Institute for Autism).
  • Brain organoids fail to reproduce some important features of the developing human cortex, which may limit their use for studying normal and disease-associated processes (Arnold Kriegstein, University of California, San Francisco).

"The advances presented today illustrate the exciting potential of using organoids to study brain processes in normal development and disease," said Hongjun Song, PhD, a professor at the University of Pennsylvania Perelman School of Medicine who studies neurogenesis and epigenetics. "However, we know they must be rigorously compared to the normally developing human brain to better understand their strengths and limitations."

This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about brain organoids on BrainFacts.org.

Related Neuroscience 2019 Presentation
Presidential Special Lecture- Understanding Cortical Development and Disease: From Embryos to Brain Organoids
Sunday, Oct. 20, 5:15 - 6:30 p.m., Hall B?

Organoids Press Conference Summary

  • Brain organoids are a promising tool for studying early human brain development in the laboratory, but they require additional characterization to understand how well they reproduce normal patterns of development.
  • If organoids can mirror the cellular and structural complexity of cells in the human cerebral cortex during development, they could be used to study both normal brain development and developmental disorders.

Individual Brain Organoids Reproducibly Generate Cell Diversity of the Human Cerebral Cortex
Paola Arlotta, paola_arlotta@harvard.edu, Abstract 278.24

  • Individual variability between brain organoids has hampered their use as experimental systems to investigate human brain development and disease.
  • A comparison of 21 organoids derived from different cell lines shows that they can consistently reproduce the rich diversity of cell types found in the human cerebral cortex. Furthermore, the identity of the different cell classes are indistinguishable when produced from different human stem cell lines.
  • Reproducible development of complex central nervous system cellular diversity can be obtained outside the context of an embryo.

Human Induced Pluripotent Stem Cell-Derived 3D Organoids Combined With High-Content Screening Reveal Network-Level Phenotypes in a Subset Of Individuals With Idiopathic Autism
Michael Nestor, mnestor@hussmanautism.org, Abstract 535.05

  • The tight balance between excitatory and inhibitory neuronal activity within brain networks is important to maintain healthy brain function, including learning and processing of sensory information. An imbalance between excitatory and inhibitory activity can lead to too much or too little firing.
  • Scientists used brain organoid structures called serum-free embryoid bodies (SFEBs) to create an "autism in a dish" model that reflected early circuit development in the human cortex.
  • Organoids created from individuals with autism tended to contain fewer inhibitory neurons than those from people without autism. They also exhibited changes in the shape of excitatory neurons, which may reflect the number and type of connections formed.
  • These results indicate that changes during brain development could lead to an imbalance of excitation and inhibition in autism.

Using Organoid Models to Study Human Cortical Development
Arnold Kriegstein, Arnold.Kriegstein@ucsf.edu, Abstract 444.03

  • Work toward the treatment of human brain disorders such as epilepsy or autism requires accurate models of the complexity of human cortical development.
  • A comparison of organoid cells to developing human brain cells found that organoid cells fail to reproduce certain important features of normal development.
  • Gene expression patterns at a series of developmental time points show that organoids contain a rich diversity of cell types that appear broadly similar to those in the developing brain but that lack the cellular and structural complexity found in developing cortex.
  • Abnormalities in cell type and development and increased cellular stress may undercut the ability of current organoid models to accurately model normal development and disease.

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About the Society for Neuroscience

The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.

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