Brain organoids were healthy and continued to grow after spending a month on the International Space Station. Credit: Jeanne Loring
When Scott Kelly returned to Earth from 340 days in space, he didn't just jump out of the spacecraft and run toward loved ones. He was placed in a chair near the landing site and taken into a medical tent. That's because microgravity is known to alter an astronaut's muscles, bones, immune system and cognition.
However, little is known about the impact of microgravity on the brain, specifically. In the search for answers, scientists from Scripps Research recently sent organoids -- tiny clumps of stem-cell derived brain cells -- to the International Space Station (ISS) for 30 days.
When the organoids returned to Earth, researchers were surprised to find them still healthy. They were also surprised to see they had matured faster than their identical counterparts grown on Earth during the space time period -- meaning the space-bound cells were closer to becoming adult neurons and even beginning to show signs of specialization.
"This lays the groundwork for future experiments in space, in which we can include other parts of the brain that are affected by neurodegenerative disease," said co-senior author Jeanne Loring, professor emeritus and founding director of the Center for Regenerative Medicine at Scripps Research.
The team used stem cells to create organoids consisting of either cortical or dopaminergic neurons, which are the neuronal populations impacted in multiple sclerosis and Parkinson's disease. Some organoids also included microglia -- a type of immune cell that is resident within the brain -- to examine the impact of microgravity on inflammation.
The Scripps researchers modified the typical organoid-growing process to avoid the need for extensive lab work on the ISS. Instead, the team pioneered a method for growing smaller-than-usual organoids in cryovials. This method was them used to prepare organoids in labs at the Kennedy Space Station before travel to the ISS in a miniature incubator.
Once all organoids were back on solid ground, the researchers compared the space-bound cells' RNA expression patterns to the identical "ground control" organoids. According to the results published in Stem Cells Translational Medicine, the organoids grown in microgravity had higher levels of genes associated with maturity and lower levels of genes associated with proliferation. Essentially, the cells exposed to microgravity developed faster and replicated less than those that remained on Earth.
The team also noted that, contrary to their hypothesis, there was less inflammation and lower expression of stress-related genes in the organoids grown in microgravity, but more research is needed to determine why. Loring speculates that microgravity conditions may more closely mirror the conditions experienced by cells within the brain compared with organoids grown under conventional lab conditions in the presence of gravity.
"There's no convection in microgravity -- in other words, things don't move," said Loring. "I think that in space, these organoids are more like the brain because they're not getting flushed with a whole bunch of culture medium or oxygen. They're very independent; they form something like a brainlet, a microcosm of the brain."
The paper published last week in Stem Cells Translational Medicine describes the team's first research space mission, but since then, they have sent four more missions to the ISS. With each one, they've replicated the conditions from the first mission and added additional experiments.
"The next thing we plan to do is to study the part of the brain that's most affected by Alzheimer's disease," said Loring. "We also want to know whether there are differences in the way neurons connect with each other in space."
Scripps is not the only organization taking advantage of the ISS's unique microgravity environment.
On Tuesday, December 17, the unpiloted SpaceX Dragon spacecraft returned from the ISS carrying nearly 50 biotechnology, physical science and student research payloads sponsored by the ISS National Laboratory.