Researchers develop ‘mini-brains’ to study neurological conditions
A team from the Johns Hopkins Bloomberg School of Public Health (MD, USA) has developed tiny brain-like structures, made up of human neurons and cells, with the potential to dramatically change how drugs for neurological conditions are evaluated.
Hundreds of thousands of test animals are used for neurological scientific research in the United States alone, but a newly developed three-dimensional ‘mini-brain’ could provide a superior level of insight into the efficacy and safety of drugs, replacing rodent brains with ‘brains’ derived from human cells.
The mini-brains are balls of human brain cells that grow and form brain-like structures over the course of 8 weeks. “95% of drugs that look promising when tested in animal models fail once they are tested in humans at great expense of time and money,” explained study leader Thomas Hartung. “While rodent models have been useful, we are not 150-pound rats. And even though we are not balls of cells either, you can often get much better information from these balls of cells than from rodents. We believe that the future of brain research will include less reliance on animals, more reliance on human, cell-based models.”
Hartung’s team created the brains using induced pluripotent stem cells; adult cells that have been reprogrammed to an embryonic stem cell-like state and then stimulated to grow into brain cells. The mini-brains were created from skin cells of healthy adults, but Hartung suggests that cells from volunteers with genetic trains or diseases could be used to create brains to study different types of pharmaceutical. The brains, Hartung added, can be used to study Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and autism. Projects testing the technology on viral infections, trauma and stoke are underway.
The mini-brains are 350 micrometers in diameter, about the size of a housefly’s eye, and hundreds of thousands of identical copies can be produced in each batch, with a hundred easily grown in the same Petri dish. After being cultivated for 2 months, the brains developed four types of neurons, as well as astrocytes and oligodendrocytes. The researchers could watch the myelin developing and observed it begin to sheath the axons. The brains also showed spontaneous electrophysiological activity, which the researchers tested by placing the brain on electrodes and listening to the electrical communication of the neurons as test drugs were added.
Hartung elaborated: “We don’t have the first brain model nor are we claiming to have the best one. But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied are as similar as possible to ensure the most comparable and accurate results.”
Hartung is applying to patent the technology, and is developing a commercial entity to produce them, with hopes to begin production in 2016. He hopes to see them used by scientists in as many labs as possible, and concluded: “Only when we can have brain models like this in any lab at any time will we be able to replace animal testing on a large scale.”