A human brain with the maturity equal to a 5-week-old fetus has been grown from adult human skin cells in a lab at Ohio State University. The brain, which is the size of a pencil eraser, contains 99 percent of the genes present in a human fetal brain.
The breakthrough will allow testing of experimental drugs before entering human clinical trials, and could completely alter our understanding of neurological diseases, such Alzheimer's.
"It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain," said Rene Anand, professor of biological chemistry and neuroscience at Ohio State. "We've struggled for a long time trying to solve complex brain disease problems that cause tremendous pain and suffering. The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents."
The main thing missing in the tiny brain is a vascular system. But what is present — a spinal cord, all major regions of the brain, multiple cell types, signaling circuitry, and even a retina — has the possibility of dramatically increasing the speed of neuroscience research, said Anand.
He developed the mini brain after encountering disappointing results studying an autism drug in rodents. "In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination," he said. "Genomic science infers there are up to 600 genes that give rise to autism, but we are stuck there. Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system – you need a human brain."
Anand converted adult skin cells into pluripotent cells, which are immature stem cells that can be nudged to become any tissue type.
"Once a cell is in that pluripotent state, it can become any organ — if you know what to do to support it to become that organ," Anand said. "The brain has been the holy grail because of its enormous complexity compared to any other organ. Other groups are attempting to do this as well."
It took Anand about 15 weeks to create the mini brain that is the equivalent of a 5-week-old fetal brain. He and his assistant Susan McKay have let the brain grow to the equivalent of a 12-week human brain, and observed how it matured during that period. "If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes," he said. "We don’t know yet."
Anand has already created mini-brain models of Alzheimer's and Parkinson's disease, and autism in a dish. They hope that once a pumping blood supply is developed, that the model could be used to study therapies for strokes. They also believe the mini brain could be used to study traumatic brain injuries and post-traumatic stress disorder.
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