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Miniature 3D brains could advance drug development for autism and more

Brain
Models of the human brain that are built from human cells are advancing research focused on finding new treatments for neurological disorders. (VSRao/Pixabay)

Organoids are living, miniature human organs that researchers use to study a range of diseases, including liver cancer and developmental disorders. But making organoids that accurately represent the human brain has proven challenging, because each person’s brain is unique.

Scientists at Harvard University and the Broad Institute say they’ve figured out how to build brain organoids that consistently mimic the cell types and neurological connections that every human brain has. They believe the organoids will be able to be used to study neurological diseases such as autism and schizophrenia, as well as the impact of drugs in the brain. They described the organoids in the journal Nature.

The researchers created organoids of the cerebral cortex, the region of the brain that governs cognition. They started with stem cell lines from both males and females and grew them in the lab for more than six months under specific culture conditions that allowed the organoids to produce all the cell types that are typically found in the cerebral cortex.

The team used RNA sequencing and big data analysis tools to study gene expression at various stages of brain development, ultimately grouping the cells by type. “Despite the different genetic backgrounds, we saw that the same cell types were made in the same way, in the correct order and, most importantly, in each organoid,” said lead author Silvia Velasco, Ph.D., a research scientist at Harvard and the Broad Institute, in a statement.

That was important, because it resulted in brain organoids that were reproducibly accurate models of the human cerebral cortex. Such organoids could be used as “controls” in experiments designed to compare normal brains with those affected by neurological diseases.

Organoids are growing in popularity as research tools, and in neurology, the technology continues to improve. Last year, a team at Tufts University used human-induced pluripotent stem cells to build 3D models of the central nervous system using a scaffold of collagen and silicon to produce cells that could mimic the electrical signals found in the human brain.

Earlier this month, the National Institutes of Health (NIH) tapped the company StemoniX for its microBrain 3D, a stem-cell-based model of the brain. The NIH plans to use the technology to test experimental treatments for opioid addiction and pain.

Thursday, the journal Science devoted a special issue to organoids, publishing several papers explaining how the technology is advancing and facilitating medical research in multiple ways. For example, one team of researchers published a review explaining how cancer organoids can be produced from tumor samples taken from patients. Such organoids could be used to test drug treatments on those specific patients with the goal of improving personalized medicine. Or, they could be used to better understand the factors that contribute to cancer, including gene mutations.

The next step for the Harvard and Broad researchers is to use their organoids to explore autism. They’re now using the gene editing system CRISPR-Cas9 to develop organoids that can serve as models of the disease.

“Not only does this advance make it immediately possible to study brain diseases, but the consistency and reproducibility is likely a first step in using organoids to begin to understand how brain functions develop—how sets of neurons ‘learn’ and ‘remember,’” said Harvard professor Doug Melton, Ph.D., co-director of the Harvard Stem Cell Institute, in the statement.

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