Novel Method Developed to Generate Pediatric Brain Organoids

 Novel Method Developed to Generate Pediatric Brain Organoids

Researchers at the Princess Máxima Center and the Hubrecht Institute have developed a novel cortex organoid that can be used to better represent the human brain during future pediatric brain cancer studies. Research utilizing these organoids will provide a deeper understanding of brain tumors and potential treatment targets.

Organoids are mini-organs that closely mimic the features of real organs and are commonly used to research diseases or potential treatments. In the research, published in Nature Communications, the researchers developed a novel cortex organoid that more closely resembles the shape, architectural organization, and various other properties of the human brain. 

The human brain is formed starting from a single structure called the neural tube, within the neural tube cells are instructed to generate the multitude of remaining cells that are present in the brain.

“The current brain organoid models generally have several developmental structures acting like an ‘independent’ small developing brain, within one organoid,” said Dr. Benedetta Artegiani, research group leader at the Máxima Center. “Researchers have tried for a long time to mitigate the formation of these multiple structures. To diminish variability, increase reproducibility, better recreate the brain’s different cellular identities, and ultimately to recapitulate brain development more closely. Now in this research, the new organoid model is composed of this self-organizing, single developing neuroepithelium.”

Named Expanded Neuroepithelium Organoids (ENOs) after the tissue used to grow them, the researchers made one key change over previous organoids. “Cells in the brain are instructed to acquire their identity through molecules that act slowly in time, the so-called temporal gradients,” said Delilah Hendriks, Oncode-researcher at the Hubrecht Institute. “This is exactly what we tried to mimic. To our surprise, it was enough to just provide one of the molecules (TGF-b) slowly step-by-step to generate brain organoids. This tiny change had an enormous impact and allowed us to generate organoids with a shape and an identity more similar to the human brain.”

The novel organoids developed by the researchers could be used to study pediatric brain tumors. The signaling molecule used to develop the ENOs is often altered in pediatric brain tumors, suggesting that cancer onset in children could alter brain development. “We can use these novel organoids as a basis to model pediatric brain tumors, and study more in depth the role of TFG-b signaling in this process,” said Artegiani. “Our research marks an essential step to create proper models to study pediatric brain cancer. If such a small change of a signaling molecule has such a great impact on brain organoid models, we can only start to imagine which effects small alterations during development can have for how pediatric brain tumors can develop.”


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