Creating a model with the brain maturity of a 5-week-old foetus, the Researchers at the Ohio State University in the US say that the dimension is almost the size of a pencil eraser, which contains 99 percent of the genes that would be there in a natural human foetal brain. Rene Anand, professor of biological chemistry and pharmacology at Ohio State and lead researcher on the brain model, said “The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed.” Before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders, such a system will allow ethical and more rapid and precise testing of experimental drugs. “It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain.” “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.” Four years ago, Anand turned to stem cell engineering after his specialized field of research, which is determining the relationship between nicotinic receptors and central nervous system disorders, ran into trouble using rodent specimens. Even then, Anand and his colleagues succeeded with their proprietary technique despite having limited funds, which they are in the process of commercializing. The brain that they have developed is a virtually complete recreation of a human foetal brain. However, the most important thing that is missing in this model, according to Anand, 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 capability to dramatically increase the pace of neuroscience research. To develop the model, Anand used methods to identify differences between 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. According to the researchers, it takes 15 weeks to build a model system to develop to be equivalent to a 5-week-old foetal human brain. Anand and McKay have let the model continue to grow to the 12-week point, watching the expected maturation changes during that period. The longer the maturation process the more complete the organoid will become. “If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes. We don’t know yet,” said Anand. “In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination,” said Anand. “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.” This week at the Military Health System Research Symposium, Anand and McKay presented the research that used brain organoid models of Alzheimer’s and Parkinson’s diseases and autism in a dish.
