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Science Fiction Meets Neuro-Reality: Organoids to Rebuild the Brain

A brain organoid derived from human induced pluripotent stem cells that displays nuclei of cells (blue) and layers of cerebral cortex (red and green).

Computer-augmented brains, cures to blindness, and rebuilding the brain after injury all sound like science fiction. Today, these disruptive technologies aren’t just for Netflix, “Terminator,” and comic book fodder — in recent years, these advances are closer to reality than some might realize, and they have the ability to revolutionize neurological care.

Neurologic disease is now the world’s leading cause of disability, and upwards of 11 million people have some form of permanent neurological problem from traumatic brain injuries and stroke. For example, if a traumatic brain injury has damaged the motor cortex — the region of the brain involved in voluntary movements — patients could become paralyzed, without hope of regaining full function. Or some stroke patients can suffer from aphasia, the inability to speak or understand language, due to damage to the brain regions that control speech and language comprehension.

Thanks to recent advances, sometimes lasting neurologic disease can be prevented. For example, if a stroke patient is seen quickly enough, life-threatening or -altering damage can be avoided, but it’s not always possible. Current treatments to most neurologic disease are fairly limited, as most therapies, including medications, aim to improve symptoms but can’t completely recover lost brain function.

H. Isaac Chen, MD

H. Isaac Chen, MD, an assistant professor of Neurosurgery at the Perelman School of Medicine and a neurosurgeon at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, is working to address this challenge. Chen calls the effort to improve how people function neurologically — instead of addressing disease symptoms — “the holy grail of clinical neuroscience.”

“This quest drives my entire academic career — being able to treat patients who don’t really have other options right now by repairing the brain,” Chen said. “While there are efforts to try to prevent disease and damage, there will always be patients who end up with permanent neurological problems. Currently, when someone has Parkinson’s disease, a brain injury, or stroke, their life is forever altered. But if we had something to improve how patients function, it’s a game changer not just for these people, but for society as a whole.”

Chen suspects that implanting neural tissue like a brain organoid could rebuild brain circuitry. His research is focused on the cerebral cortex — the part of the human brain that sets us apart from other animals. The cerebral cortex supports basic functions such as movement, visual sensation, and higher-order cognitive processes, like working memory and the ability to plan.

Chen likens his approach to fixing a computer. The cortex has repetitive units called cortical columns, the basic processing units of the cortex. In this analogy, imagine the brain is a computer and the cortex is made up of millions of processing units, repeated over and over, allowing for “computation” — how we think or do things. Chen’s theory is that if some number of the brain’s “processors” (the cortical columns) is taken out of action, you can replace the damaged processors with the new ones, resuming the brain’s function, just as you would do with a computer.

Chen’s hope is to use brain organoids or other similar neural tissues to create these artificial cortical processors in the lab, and insert them into the brain when there is a problem — thereby replacing the bad processors in the brain.

“Brain organoids are the only lab-based platform that recreates the architecture of the human brain to any significant degree, which is why there’s been so much excitement around them lately. However, these brain organoids aren’t perfect right now — they don’t look exactly like the cortex and can’t function exactly like it. But we’re making strides in the right direction,” Chen said.

To push this idea forward, there’s an effort underway to understand how brain organoids can become part of the brain. Chen is currently focused on the visual cortex, analyzing how brain organoids connect to the visual system of rats and how they respond when the animal sees patterns of light. Remarkably, when light is aimed into the rat’s eye, neurons in the organoid become active, signaling that these cells are communicating with the rat’s own brain cells.

“We’re starting to see some glimmers of hope in our experimental studies that this can work. It will take years to get to where we want to go, but to see initial evidence of success is extremely exciting,” Chen said. 

Stay tuned for more examples of futuristic-seeming brain technology and advances in the next post on the Penn Medicine News Blog.

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