3D image of brain organoid, showing the stem cells in yellow and the neurons in magenta. Credit: Benedetta Artegiani, Delilah Hendriks, Anna Pagliaro
Key points:
- Researchers created pediatric brain organoids with features that more closely mimic the real-life version.
- The biggest advancement is a new cortex organoid that can be used as a basis to model pediatric brain tumors.
- The new models will allow scientists to better understanding of how brain tumors arise and develop could help researchers in finding possible targets for treatment.
Researchers at the Princess Máxima Center for Pediatric Oncology and the Hubrecht Institute have created organoids with features that more closely mimic the real-life version, including shape, architectural organization, and several properties of cells. The biggest advancement is a new cortex organoid that can be used as a basis to model pediatric brain tumors.
Multiple childhood brain tumors, like cortical gliomas, arise from the cortex, the outer layer of the largest part of the brain and the brain’s most expanded structure.
The current brain organoid models generally have several developmental structures acting like independent small developing brains, within one organoid. Researchers have tried for a long time to mitigate the formation of these multiple structures.
To generate these new organoids, researchers made a small but important change.
“Cells in the brain are instructed to acquire their identity through molecules that act slowly in time, the so-called temporal gradients. This is exactly what we tried to mimic,” explains research group co-leader Delilah Hendriks. “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 signaling molecule that the researchers used to make the organoids is often altered in childhood brain tumors, suggesting that the onset of cancer in young children could be linked with changes in brain development.
Now that the researchers understand that temporal gradients are of great importance to generate more accurate organoids, this study paves the way to develop brain organoids more and more similar to the developing human brain.
“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 what effects small alterations during development can have for how pediatric brain tumors can develop,” said research co-leader Benedetta Artegiani.