Human Brain Organoids Grown in Rats to Study Neurological Diseases

Researchers from Stanford University cultivated stem cells into three-dimensional clumps of tissue to make tiny blobs of lab-grown human brain cells measuring just a few millimeters in diameter. These tissues are called brain organoids that contain some of the cells and properties of the human brain, offering insights into the development of neurological diseases.

Previous experiments that tried transplanting them into rodents' brains failed to integrate them into the animals' brains. But this time, it worked, and the brain organoids formed connections, signaling that these bundles of cells could become more sophisticated.

Making Lab-Grown Human Brain Organoids

Dr. Sergiu Pasca, the senior author of the study, to the Associated Press that many neurodevelopmental disorders are likely unique to humans, but the human brain is not very accessible. That is why approaches that do not involve taking brain tissues are promising avenues for tackling these conditions.

Researchers used their previous work to create brain organoids, tiny structures resembling human organs that could also represent others like the liver, kidneys, and prostate.

To grow lumps of brain-like tissues, they used a technique that earned the Nobel prize in medicine in 2012. Stanford researchers turned skin cells into blank slates called iPS cells, a form of stem cell that can be turned into any cell of the body using chemical cues.

These cells were then multiplied to form organoids resembling the human brain's outermost layer or cerebral cortex, which plays a key role in memory and thinking—learning, reasoning, and emotions.

The brain organoids are three-dimensional clumps that start to communicate and signal each other. Making them is part of the movement to create miniature versions of the body's organs to study diseases, possible test treatments, and supply replacements for transplants. They could be ideal targets of study for modern neuroscience that are too invasive if done in real human brains.

Transplanting the Brain Organoids to Rats

Stanford researchers transplanted the brain organoids into the somatosensory cortices of newborn rats, a part of the brain that processes sensory information, Wired reported. They observed it over several months and watched as it grew to occupy about one-third of the hemisphere of rat brains.

Assistant Professor H. Isaac Chen of the University of Pennsylvania and his colleagues previously tried similar experiments in adult rodents but failed. In their latest attempt, they took advantage of the early development of a young rat's neuronal circuits as they are more plastic.

The transplanted human organoids grew nerve fibers that extended into the rat's brain tissue and formed synapses between neurons. These connections do not exist in brain organoids grown in a dish, which limits the opportunity to transplant organoids in living animals.

Furthermore, the team also grew some of their organoids from the cells of patients with the Timothy syndrome genetic disease, which often causes neurodevelopmental delays in autism. These organoids developed abnormal dendrites when transplanted into rats. These defects were not seen in earlier organoid experiments in other animals.