In a breakthrough, scientists, including one of Indian-origin, have developed the most complete laboratory-grown human brain ever, after creating a model that equals the brain maturity of a 5-week-old foetus.
Scientists at The Ohio State University developed the brain, about the size of a pencil eraser, which has an identifiable structure and contains 99 per cent of the genes present in the human foetal brain.
“The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed,” said Rene Anand, professor of biological chemistry and pharmacology at Ohio State.
Such a system will enable ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders.
“It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain,” Anand said.
“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,” he said.
Anand said the main thing missing in this model is a vascular system. A spinal cord, all major regions of the brain, multiple cell types, signalling circuitry and even a retina are present and have the potential to dramatically accelerate the pace of neuroscience research.
To develop the model, Anand used techniques to differentiate pluripotent stem cells into cells that are designed to become neural tissue, components of the central nervous system or other brain regions.
“We provide the best possible environment and conditions that replicate what’s going on in utero to support the brain,” he said of the work he completed with colleague Susan McKay, a research associate in biological chemistry and pharmacology.
High-resolution imaging of the organoid identifies functioning neurons and their signal-carrying extensions – axons and dendrites – as well as astrocytes, oligodendrocytes and microglia.
The model also activates markers for cells that have the classic excitatory and inhibitory functions in the brain, and that enable chemical signals to travel throughout the structure.
It takes about 15 weeks to build a model system developed to match the 5-week-old foetal human brain. Anand and McKay have let the model continue to grow to the 12-week point, observing expected maturation changes along the way.
“If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 per cent of missing genes. We don’t know yet,” he said.
He and McKay have already used the platform to launch their own projects, creating brain organoid models of Alzheimer’s and Parkinson’s diseases and autism in a dish.