It may sound like a special effect engineered for the silver screen, but it’s a reality in Brigham and Women’s Hospital (BWH) labs: mini brains, grown from human stem cells, that let researchers manipulate genes to study how certain mutations lead to mental illness.
These 3-D brain models, known as cerebral organoids, are crucial to research seeking to understand the genetic origins of conditions such as schizophrenia, bipolar disorder, and depression. They’re created from patient blood samples, from which specific types of stem cells can be extracted and “directed” to become any type of cell in the body. From there, the research team disrupts DISC1, the specific gene linked to mental illness, to model the mutation seen in families with these conditions. Those with a mutated form of the gene have shown significant disruptions in brain structure compared to those without the mutation.
“Compared to traditional methods that have allowed us to investigate human cells in culture in two dimensions, these cultures let us investigate the three-dimensional structure and function of the cells as they are developing, giving us more information than we would get with a traditional cell culture,” says senior study author Tracy Young-Pearse, PhD, head of the Young-Pearse Lab in the Ann Romney Center for Neurologic Diseases at BWH where the research is centered.
These discoveries could eventually give way to new treatment approaches for mental health conditions. The modified mini-brains also showed increased signaling in a neural pathway known to be important for giving the brain the correct shape and organization, and one that is disrupted in bipolar disorder. By blocking this pathway in the modified mini-brains, researchers were able to “rescue” them to give them a structure similar to that of the mini-brains grown from normal stem cells. This suggests that the pathway studied, known as the WNT pathway, could be a target for new therapies—giving this futuristic research life-changing potential for the millions of Americans affected by these disorders.
More in the BWH Bulletin.