Lab Grown ‘Mini Brains’ Shed Light on Zika’s Disastrous Effects

This new study confirms the virus’ terrible effect on the fetal cortex.

|
Apr 23 2016, 2:00pm

The SpinΩ bioreactor used to create the conditions for mini-brains to grow.Image: John Hopkins Medicine

Researchers from Johns Hopkins University have confirmed one of the most important ways that Zika causes microcephaly in the brains of infants via an innovative new technology, according to a study published Friday in Cell.

By growing realistic brain organoids (groups of tissue meant to mimic actual organs) inside 3D printed bioreactors (vessels in which the brains are grown) the researchers confirmed that Zika infects specialized stem cells responsible for building the cerebral cortex, the outer layer of the brain. Zika then turns these cells into virus factories.

The mini brains consisted of many different kinds of cells mixed together Xuyu Qian, the lead author of the paper and a PhD candidate at Johns Hopkins University told me. His team's work showed that the virus prefers attacking neurological stem cells—the kind found in the cranium of developing fetuses—over other types.

"In this paper we confirmed the preferential target of the virus," Qian said.

Their work also showed that the extent of the damage caused by Zika differs depending on when cells are infected.

The "mini brains" survive for up to 100 days according to the study, allowing the researchers to examine what happens when a mother is infected very early and towards the middle of her pregnancy. Their work supported other clinical findings that suggest babies are most at risk during their first trimester, although there are still disastrous effects later in a mother's pregnancy.

A mini-brain infected with Zika virus. The virus is shown in green, vulnerable neural progenitor cells are shown in red, and neurons are shown in blue.

Image: Johns Hopkins Medicine

The researchers grew the "brains" using human stem cells. A number of researchers in different fields have grown tiny organs for years, but the process is typically incredibly difficult due to the complexity of various organs and the high cost of the nutrients needed to cultivate human stem cells in the lab.

In order to help overcome these hurdles, several high school students who spent a summer working in the Johns Hopkins University School of Medicine's Institute for Cell Engineering came up with the idea for a smaller 3D printed bioreactor that would require less nutrients than the larger, commercially available options.

After three years of testing different prototypes, the researchers were finally able to develop one that provided a suitable environment for the development of tiny brains. Dubbed SpinΩ, the paper's authors included plans for it in their work, so that it could be recreated in other labs. "The design isn't sophisticated, but it's very intuitive," Qian said.

"This technology is not restricted to the Zika virus, it can be used to study all sorts of developmental disorders," Qian told me. In the future, he hopes to commercialize the bioreactor that his team created in order to lower its price. "We hope it becomes a standard model for studying human development," he said.