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 whatâs seen in a 40-day-old human fetus, and may soon allow for better, more effective drug treatments for diseases like Parkinsonâs and Alzheimerâs.
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 âmindsâ 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 arenât intended to simply be impressive laboratory tricksâthese 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.
âMost brain organoids that you see in papers are one brain region, like the cortex or the hindbrain or midbrain,â 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 thatâs easier said than done.
âWe need to study models with human cells if you want to understand neurodevelopmental disorders or neuropsychiatric disorders, but I canât ask a person to let me take a peek at their brain just to study autism,â said Kathuria. âWhole-brain organoids let us watch disorders develop in real time, see if treatments work, and even tailor therapies to individual patients.â
After years of experimentation, Kathuria and colleagues became one the worldâs 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 âbiological superglueâ that fostered connections between the tissues. As these meshed, the regions began generating electrical activity as a unified network. The studyâs authors even noted the formation of an early blood-brain barrierâthe brainâs surrounding cell layer that controls what molecules can and cannot enter.
These MRBOs are much smaller than a human brain, with each one containing 6â7 million neuronsâby 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, 85â90 percent of all medications fail during Phase 1 clinical trialsâa 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.
â[S]chizophrenia, autism, and Alzheimerâs affect the whole brain, not just one part of the brain,â said Kathuria. âIf you can understand what goes wrong early in development, we may be able to find new targets for drug screening.â
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