Biomedical engineers have achieved a major breakthrough in organoid research, pushing us closer to a new era of neurophysiological analysis and treatments. A team at Johns Hopkins University has created some of the first whole-brain organoids that include interconnected, functional tissues from each region of the human brain.Â
According to their paper published in the journal Advanced Science, these neuronal cell masses display activity similar to what’s seen in a 40-day-old human fetus, and may soon allow for better, more effective drug treatments for diseases like Parkinson’s and Alzheimer’s.
Brain organoid development is one of the most promising, complex, and often surreal biomedical frontiers. Derived from pluripotent human stem cells, these lab-grown cultures function as rudimentary “minds” that lack sentience but retain basic cognitive functions like memory and learning. Although initially limited by their two-dimensional designs, newer three-dimensional compositions are already capable of playing rudimentary games of Pong and powering small robots.
Such demonstrations aren’t intended to simply be impressive laboratory tricks—these complex, customizable cell blobs could kickstart a new era of neuropsychiatric research and treatment, brain-computer interfaces, and even wholly novel forms of artificial organoid intelligence. For years, however, the field of study has been limited by a lack of complexity.
“Most brain organoids that you see in papers are one brain region, like the cortex or the hindbrain or midbrain,” biomedical engineer and study lead author Annie Kathuria said in a statement.
Ideally, Kathuria and colleagues would observe every region of the brain working in tandem so that they can study neurodevelopment holistically. But that’s easier said than done.
“We need to study models with human cells if you want to understand neurodevelopmental disorders or neuropsychiatric disorders, but I can’t ask a person to let me take a peek at their brain just to study autism,” said Kathuria. “Whole-brain organoids let us watch disorders develop in real time, see if treatments work, and even tailor therapies to individual patients.”
After years of experimentation, Kathuria and colleagues became one the world’s first teams to grow what they call a multi-region brain organoid (MRBO). To do this, researchers first grew neural cells from separate brain regions along with basic blood vessels in an array of lab dishes. Next, they attached the individual regions together using sticky proteins described as a “biological superglue” that fostered connections between the tissues. As these meshed, the regions began generating electrical activity as a unified network. The study’s authors even noted the formation of an early blood-brain barrier—the brain’s surrounding cell layer that controls what molecules can and cannot enter.
These MRBOs are much smaller than a human brain, with each one containing 6–7 million neurons–by comparison, an adult brain contains tens of billions of neurons. But with 80 percent of the cells normally seen in early fetal brain development, they offer an unprecedented opportunity for analysis. For example, using MRBOs in experimental drug trials could help improve success rates. According to the team at Johns Hopkins, 85–90 percent of all medications fail during Phase 1 clinical trials—a rate that nears 96 percent for neuropsychiatric drugs. This is largely due to the fact that most biomedical researchers currently rely on animal models during early development stages. Swapping out lab rats for whole-brain organoids that more closely resemble a natural human brain will likely offer quicker, better results.
“[S]chizophrenia, autism, and Alzheimer’s affect the whole brain, not just one part of the brain,” said Kathuria. “If you can understand what goes wrong early in development, we may be able to find new targets for drug screening.”
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