If you haven’t been living under a rock for the past year, you’ve been hearing – and possibly worrying – a lot about the Zika virus. While it isn’t much of a concern for healthy adults, it can have devastating effects on unborn children whose mothers have been infected. Brain abnormalities including microcephaly, a condition resulting in an underdeveloped brain and abnormally small head, have affected thousands of babies in South America since the virus began spreading last year, and the World Health Organization has warned that the disease is likely to begin spreading across the world as warm weather hits in and “mosquito season” starts in Europe and North America. The WHO has declared Zika to be a global health emergency, and scientists are scrambling to try to understand the disease and, hopefully, develop some kind of treatment or vaccine. Fast.
As it turns out, 3D printing can help. Researchers at Johns Hopkins University have used the technology to create tiny pinhead-sized brains which were then infected with the virus, allowing them to study exactly how Zika attacks the brain. The research team, led by professors Guo-li Ming and Hongjun Song, was responsible for an earlier study that revealed that Zika kills off neural stem cells in the brains of developing fetuses. However, that study utilized 2D tissue culture, which limited what the researchers were able to discover about brain development.
The more recent study, which has been published in the journal Cell, was carried out by 3D printing miniature spinning bioreactors, which were used to produce several mini-brains, also known as organoids, from human stem cells. Organoids have been used in medical research for years, but they’re highly expensive to create. The 3D printed bioreactors enabled the Johns Hopkins team to produce a large number of the tiny brains for a much lower cost.
Three types of neural tissue was produced for the study: forebrain, midbrain and hypothalamus tissue, which was capable of surviving in the lab up to 100 days. This gave the team plenty of time to study the brains as they developed, and the findings from the 2D study were confirmed: Zika does its damage by attacking neural stem cells and stunting the growth of the cortex, the outer layer of the brain which is largely responsible for attention and memory. The study also confirmed that a developing fetus is most at risk in the first trimester.
“Studies of fetuses and babies with the telltale small brains and heads of microcephaly in Zika-affected areas have found abnormalities in the cortex, and Zika virus has been found in the fetal tissue,” said Dr. Ming. “While this study doesn’t definitely prove that Zika virus causes microcephaly, it’s very telling that the cells that form the cortex are potentially susceptible to the virus, and their growth could be disrupted by the virus.”
So what comes next? Currently, the team is testing FDA-approved compounds on the organoids in hopes that one of them might have an effect on the virus, and they’re also going to be publishing the files for the 3D printed bioreactors so that other scientists can generate organoids to study and test. In a health crisis situation, it’s all hands on deck.
“Now that we know cortical neural progenitor cells are the vulnerable cells, they can likely also be used to quickly screen potential new therapies for effectiveness,” said Dr. Song.
In the long term, the bioreactors could lead to new treatments for other neurological diseases; for example, according to Dr. Song, director of the stem cell research program at John Hopkins Medicine Institute for Cell Engineering, the reactors could be used to grow new neurons to replace the ones that die off in patients with Parkinson’s disease.
“This is the next frontier of stem cell biology,” he said.
Researchers from Florida State University and Emory University also participated in the study. Authors credited in Cell include co-first authors Xuyu Qian and Ha Nam Nguyen, as well as Mingxi M. Song, Christopher Hadiono, Sarah C. Ogden, Christy Hammack, Bing Yao, Gregory R. Hamersky, Fadi Jacob, Chun Zhong, Ki-jun Yoon, William Jeang, Li Lin, Yujing Li, Jai Thakor, Daniel A. Berg, Ce Zhang, Eunchai Kang, Michael Chickering, David Nauen, Cheng-Ying Ho, Zhexing Wen, Kimberly M. Christian, Pei-Yong Shi, Brady J. Maher, Hao Wu, Peng Jin, Hengli Tang, Hongjun Song, and Guo-li Ming.[Sources/Images: Cell, Sky News ; MNT]