Researchers at Johns Hopkins University School of Medicine’s Institute for Cell Engineering have used new mini-brain technology to study the ravages of the Zika virus on the brains of unborn children.
Using a new type of pinhead-size, laboratory-grown mini-brains for scientific research will revolutionize the field of brain research and has already helped with confirming Zika.
Researchers in a number of fields have been growing tiny organs from human stem cells to gain better insight into disease development. Existing techniques to grow and work on mini-brains were limited because of the complexity involved, as the mini-brains are the size of a pinhead and the bioreactors, the equipment they are grown in is the size of a soda can. Because of the bioreactor’s size, the cost of nutrients to grow stem cells in the lab and the expense of chemical growth factors that guide the tissue to organize itself into a brain is expensive. Few labs could afford to grow enough mini-brains to be useful in research.
The researchers’ son and two other high school students from New York and Texas on a summer internship created a solution. They had the idea of creating a bioreactor with a 3D printer. They came up with a bioreactor that fit over commonly-used 12-well laboratory plates that could spin the liquid and cells inside like a centrifuge, at the right speed to create brains. They called their invention Spin Ω. So far, it has been used to create brains mimicking the front, middle and back of a human brain. They also created a forebrain with six layers of brain cells, the types found in the human cortex for the Zika study.
Hongjun Song, PhD, professor of neurology and neuroscience at Johns Hopkins University School of Medicine’s Institute for Cell Engineering says,
We have been working for three years to develop a better research model of brain development, and it’s fortunate we can now use this one to shed light on the major public health crisis posed by the Zika infection. This more realistic, 3D model confirms what we suspected based on what we saw in a two-dimensional cell culture: that Zika causes microcephaly, abnormally small brains and heads, mainly by attacking the neural progenitor cells that build the brain and turning them into virus factories.
Song’s wife and research partner, Guo-li-Ming, MD, PhD and professor of neurology, neuroscience, psychiatry and behavioral science at Johns Hopkins, adds,
One thing the mini-brains allowed us to do was to model the effects of Zika virus exposure during different stages of pregnancy. If infection occurred very early in development, the virus mostly infected the mini-brains’ neural progenitor cells, and the effects were very severe. After a while, the mini-brains would stop growing and disintegrate. In a later stage, mimicking the second trimester, Zika still preferentially infected neural progenitor cells, but it also affected some neurons. Growth was slower, and the cortex was thinner than non-infected brains.
This research corresponds to what clinicians have witnessed in infants born to women who contracted Zika during their pregnancy. The earlier in pregnancy that Zika occurs, the more severe its effects.
The hope is that the new bioreactor system of growing mini-brains will lead to its use in drug trials, the study of brain development and other disorders. Song says that in the future, it can be used to grow dopa minergic neurous for transplant to replace those that die off in Parkinson’s patients.
The recent research paper includes the files for 3D printing the Spin Ω so that researchers anywhere can create their own bioreactors. Unlike the cost-prohibitive predecessor, the new bioreactor can be created for just a few hundred dollars in materials.
Song sums up,
This is the next frontier in stem cell biology.
For more information, go to a previously written article on this subject at Mysterious Universe.