STANFORD Stanford scientists have grown and assembled parts of a humanbrainin a dish.

Heres what is even more remarkable: Their mini-brain forms mental circuitry and cells converse with each other.

There is cross-talk, said lead researcher Dr. Sergiu Pasca, assistant professor of psychiatry and behavioral sciences at Stanford University School of Medicine, whose study was published in the journal Nature.

The team did not build an entire brain, the stuff of sci-fi fantasy. It doesnt think; its not self-aware. Thats a far more complex and likely unattainable goal.

Instead, they made a tiny but powerful model of the cerebral cortex for the study of such devastating human disorders as schizophrenia, epilepsy and autism impairments not easily studied in people.

This mini-brain reveals how networks of our mind can grow, behave and communicate, giving scientists an unprecedented view of our most mysterious organ.

What goes wrong with the mental circuitry of people with disease or disorders? Thats what they hope to learn.

Their brain also can be used to test potential drugs, essential for improving the pharmaceuticals need by psychiatry.

Its the first example of assembling, in a 3D culture, this brain region, Pasca said. Essentially, we get a small cerebral cortex in a dish.

The neurobiology of the brain remains one of the great challenges of modern medicine. Thats because we havent had direct views of the brains cellular behavior. While we can watch mental function through tools like Magnetic Resonance Imaging, that doesnt show us whats happening at the most basic level.

And we havent been able to watch brain development in the lab, because it happens during the second and third trimester of pregnancy.

Other diseases, like cancer, dont have this problem. Thats because doctors can sample tumor cells and look at them under a microscope. The sampling and study of brain cells is much harder.

Recapitulation of a pivotal stage in the cortexs formation demonstrates the techniques promise for discovery and even for testing potential interventions, according to a statement by Dr. Joshua Gordon, director of the National Institute of Mental Health, which made a videoto explain theresearch. It moves us closer to realizing the goal of precision medicine for brain disorders.

Members of the Stanford team started with longstanding tried-and-true techniques. They took skin cells and turned them into stem cells. Then they used chemical prods to turn them into two different types of brain cells.

In one dish, they grew cells called glutamatergic neurons, because they secrete the chemical glutamate, responsible for sending excitatory messages in the brain. Too much cellular excitement is thought to underlie conditions ilke seizures in epilepsy.

In a second dish, they grew cells that secrete a different chemical, called GABA, which sends inhibitory messages in the brain. Their job is to apply the brakes.

These arent just flat garden-variety layers of cells. Rather, theyre brainballs. Each ball measures about 1/16 of an inch in diameter and consists of over 1 million cells each, living for up to two years. They dont adhere to the dish; rather, they float, like little bobbing pearls.

Then they were introduced to each other.

And heres the magic: Within three days, the two cell types fused into one big sphere and then started organizing.

The cells that make GABA cells migrated over to the cells that make glutamate and began forming the circuitry that is responsible for the brains most advanced cognitive activities, the team found.

They start moving, and keep moving, for months, making small hops in one direction, said Pasca. They move to the other side and make connections.

They grew long appendages called axons. They also grew little knobby spines that stick out like branches to receive chemical messages from other cells axons. It is this signaling that enables us to think and learn.

Using small electrodes, the team listened in on the fused cells, and heard communication. The GABA-making and glutamatergic cells were successfully forming circuits and signaling to each other.

To be sure, their brainball is an incomplete model. It lacks complexity and is missing other cells that are part of the cerebral cortex. There arent blood vessels. It will never grow large.

But it is a powerful platform for asking how the human brain develops, said Pasca. Can we find abnormalities that are associated with disease? If we do, can we test drugs? That is its potential.

Already, its taught them about a rare developmental disease called Timothy syndrome, which includes symptoms of autism and epilepsy. Growing brainballs from skin cells donated by three patients, they found that these cells dont migrate normally their hopping movements are too quick, and too small. Over time, they got left behind.

The same gene that causes Timothy syndrome is linked to schizophrenia, other types of autism and bipolar disease. Pasca suspects these conditions may also have flaws in the fusing and communication of cells.

In the future, the Stanford team hopes to study the cells of individual patients to see if they can detect problems with their ability to move, migrate and communicate.

Stanfords Office of Technology Licensing has filed for a patent on the intellectual property involving the generation of these spheres and their assembly for studying development and disease.

The exquisite timing and placement of these different neuron cell types is critical for establishing a balance between excitation and inhibition within brain circuits. This balance is thought to be disrupted in brain disorders, Dr. David Panchision, chief of the NIMH Developmental Neurobiology Program (which funded the research), said in a statement. Re-playing these developmental processes with a patients own cells can allow us to determine what distinguishes these different disorders at a molecular and cellular level.

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Human brain in a dish: Stanford-grown brain cells fuse and chat - The Mercury News

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