Apr 25, 2016 | By Alec

Though it hasn’t been in the news quite as much in recent weeks, the Zika virus is still a huge problem throughout South America. Deemed a global public health emergency by the World Health Organization, thousands of babies have already been born with underdeveloped brains since the outbreak of the virus about a year ago. Most importantly, no cure has yet been found. However, a team of scientists from the Johns Hopkins University in Baltimore have just realized an important step in the right direction. Using 3D printed and lab-grown ‘mini-brains’ that were artificially infected with the virus, they have found out exactly how the virus causes microcephaly – stunted head and brain development – in developing fetuses.

Both the findings and this unusual 3D printing application were revealed in a paper in the latest edition of the journal Cell. The study was spearheaded by husband and wife team Guo-li Ming (professor of neurology, neuroscience, and psychiatry and behavioural sciences at Johns Hopkins) and Hongjun Song, (professor of neurology and neuroscience).

In a nutshell, they have developed the SpinΩ, a new bioreactor for 3D bioprinting applications that can be used to build cost-effective brain models the size of a pinhead. As professor Song explained, they had been looking for better brain research models for three years, and it just so happened that their solution could be used to shed light on the Zika virus. “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,” he said.

Specifically, they found that Zika infects specialized stem cells in the cortex layer of a fetus brain – an area of crucial importance for perception, attention, memory and consciousness. Thanks to the 3D printed mini-brains, they were even able to see exactly what happened if infection occurred at different stages of a pregnancy. “If infection occurred very early in development, the virus mostly infected the mini-brains' neural progenitor cells, and the effects were very severe,” said Ming. “After a while, the mini-brains would stop growing and disintegrate. At a later stage, mimicking the second trimester, Zika still preferentially infected neural progenitor cells, but it also affected some neurons.”

An infected brain, with the Zika virus visible in green.

These results closely correspond to what has been seen in infants born to women who caught the virus during pregnancy. It proves that the earlier the infection occurs, the more severe its effects are. While this doesn’t point to a cure yet, furthering our understanding of the infection process is an important step in the right direction. The next step would be to test FDA-approved drugs intended for other brain diseases on the mini-brains, to see if they offer some level of protection.

As the researchers revealed, they actually found inspiration for the SpinΩ in the work of three high school students who spent a summer working in the lab. Their son, and two other students, had been experimenting with the in-house 3D printers and came up with a concept for a superior bioreactor that would fit over commonly used 12-well laboratory plates. This bioreactor would simultaneously spin around the liquid and cells inside at just the right speed to allow brain formation.

A concept image of the bioreactor.

Before this breakthrough, 3D bioprinting was hardly suitable for brain studies. As professor Song explained, the brain’s complexity required relatively large bioreactors and large quantities of chemical growth factors. This made 3D bioprinted brain models far too expensive. The few labs who could afford to make enough mini-brains for research purposes also could not yet specifically focus on different parts of the brain. The new SpinΩ bio-reactor is far more efficient, though graduate student Xuyu Qian and postdoctoral fellow Ha Nam Nguyen spent years determining the optimum speed factors and chemical processes.

So far, the SpinΩ has been used to build three types of 3D printed mini-brains: brains that mimic the front, middle and back portions of a human brain. The forebrain model was used for their study of the Zika virus. “This is the next frontier of stem cell biology,” argued Song, who added that the same type of mini-brains could be used for studies on Parkinson’s disease and other brain (development) disorders. To facilitate that research, 3D printable SpinΩ files have been included in the their paper, which can be found here. The SpinΩ, they add, can be built by other researchers for just a few hundred dollars.



Posted in 3D Printing Application



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mprend wrote at 4/26/2016 5:15:29 PM:

Really interesting reseach! A small correction - the organoid models were not bioprinted. The bioreactor used in the study is 3D bioprinted, but the 3D cultures were created manually.

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