Brain model with maturity of 5-week-old fetus grown in a lab
Researchers at Ohio State University (OSU) have grown a nearly complete human brain equivalent in size and structure to that of a five-week old fetus. Called a "brain organoid," it was bioengineered using adult human skin cells and is the most advanced human brain model yet created in a laboratory.
The lab-grown fetal brain model is the result of four years of research by Rene Anand, professor of biological chemistry and pharmacology at OSU, and Susan McKay, a research associate in biological chemistry and pharmacology, aimed at finding a better alternative to conventional rodent studies.
Its purpose is not only to provide scientists with a better research model, but also to avoid ethical concerns regarding fetal tissue research, which have been highlighted in recent weeks by allegations of illegal organ harvesting at US abortion clinics.
The organoid was developed by starting with adult skin cells and coaxing them to revert to pluripotent cells, which are a form of stem cell that can form any other type of cell in the body. These are used to build up specific tissues and then entire organs by recreating features of an in utero environment.
In this case, Anand's proprietary method produced a model fetal brain in 12 weeks that's about the size of a pencil eraser with specific structures and 99 percent of the genes normally present in a 5-week-old fetal human brain.
"If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes," says Anand.
More advanced than previous brain models, it has all the major brain regions, a spinal cord, multiple cell types, signaling circuitry, and a retina, but lacks a vascular system, so its growth potential is limited. However, it does exhibit axons, dendrites, astrocytes, oligodendrocytes, and microglia, and can transmit chemical signals throughout its structure as would a natural brain.
The researchers say that this organic modeling not only helps to address certain ethical issues, but also has the potential to provide faster and more accurate drug testing, as well as for more advanced studies of the genetic and environmental causes of central nervous system disorders.
"In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination," says 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."
To this end, Anand and McKay have already created brain organoid models of autism, as well as Alzheimer's and Parkinson's diseases, in a dish. With further development and the addition of a blood supply, the hope the platform could also be used to study stroke therapy. It could also be used for gaining a better understanding of Gulf War illness, traumatic brain injury, and post-traumatic stress disorder (PTSD).
The team also hopes to make the organoid part of DARPA's Microphysiological Systems program, which uses engineered human tissue to mimic human physiological systems.
Anand presented his findings at the 2015 Military Health System Research Symposium.
Source: Ohio State University