Organoids are helping scientists study the coronavirus.
TThe tiny drops of brain tissue that Thomas Hartung, MD, PhD, grows in his laboratory at Johns Hopkins University have little to do with it. Barely visible, they are little more than soft white spots.
Known as “mini brains” or organoids, these tiny structures made from stem cells contain neurons that spontaneously emit electrical activity like a real brain would. Those that Hartung grows resemble the brain of a human fetus at five months of development.
Hartung and his team are using brain organoids to better understand SARS-CoV-2, the virus that causes Covid-19. What they have found so far about the brain’s susceptibility to the virus is troubling: “It is bad news that adds to a pile of bad news,” says Hartung. OneZero.
Scientists have been cultivating organoids for more than a decade, but the current pandemic has generated great interest in using them to study the new coronavirus. The researchers are now conducting similar tests on miniature lungs, intestines, and livers, as well as rubber “organs on chips.”
There are many scientists who still don’t know about the virus, and laboratory animals can only tell us so much. Since many animals do not receive Covid-19 as humans do, mini human organs offer a way to learn which cells the virus can infect and how the infection damages the body. Furthermore, organoids are a faster and cheaper option than research animals because they can be mass produced by the hundreds or thousands in the laboratory. Scientists are also using mini organs as substitutes for real ones to test possible drugs to treat Covid-19.
Before Covid-19, brain organoids helped unravel another viral mystery: why some pregnant women who became infected with the Zika virus gave birth to babies with smaller brains and heads. When scientists exposed mini-brains to Zika, they discovered that still-developing neurons were especially susceptible to the virus.
After Hartung and his colleagues read reports of some Covid-19 patients experiencing neurological symptoms in addition to respiratory symptoms, they wanted to know if SARS-CoV-2 could also infect brain cells.
It was the job of C. Korin Bullen, a postdoctoral researcher at Johns Hopkins Medicine, to find out. To work with the dangerous live virus, he put on a protective suit, shoe covers, gloves with adhesive tape on his wrists, and a hooded mask. He then entered a biosecurity laboratory, where he exposed the brain organoids to the coronavirus.
What he discovered was that the virus could infect the mini brains and, 72 hours later, it began to multiply within them, suggesting that human brain cells are susceptible to the virus. The results were published online June 26 in the journal. ALTEX: Alternatives to animal experimentation.
“This means that the virus has the potential to infect human brain cells, which is very much in line with the many neurological symptoms seen in patients,” says Hartung. Problematically, he says, some of the cells in the brain’s organoids contained hundreds of virus particles.
The findings shed light on why Covid-19 appears to attack the brain in some people. At Journal of the American Medical Association On April 10, Chinese researchers reported that about 36% of 214 Covid-19 patients at a Wuhan hospital had neurological symptoms in addition to respiratory symptoms. And a study published on July 8 in the magazine. Brain He found that the neurological complications of Covid-19 can include delirium, brain inflammation, stroke, and nerve damage.
How the virus causes these symptoms is still unknown. The possibility that SARS-CoV-2 could cross the blood-brain barrier, the protective border designed to keep toxins and pathogens out of the brain, could have implications for drug development. To effectively treat Covid-19 patients with neurological symptoms, Hartung says he may need a medication that can cross the blood-brain barrier. Not all drugs can.
The Johns Hopkins study also raises concerns for pregnant women. Like real human brains, mini brains contain the same receptor, called ACE2, which allows the virus to enter lung cells. While there is still no evidence that the virus causes miscarriage, birth defects, or developmental disorders, Hartung says the possibility cannot yet be ruled out.
