Microgravity is known to alter muscles, bones, the immune system, and cognition, but little is known about its specific impact on the brain. To discover how brain cells respond to microgravity, Scripps Research scientists, in collaboration with the New York Stem Cell Foundation, sent small clusters of stem cell-derived brain cells called “organoids” to the International Space Station (ISS).
Surprisingly, the organoids were still healthy when they returned from orbit a month later, but the cells had matured faster compared to identical organoids grown on Earth: they were closer to becoming adult neurons and were beginning to show signs of specialization. The results, which could shed light on the possible neurological effects of space travel, were published on October 23, 2024 in Stem cell translational medicine.
“The fact that these cells survived in space was a big surprise,” says co-senior author Jeanne Loring, PhD, professor emerita in the Department of Molecular Medicine and founding director of the Scripps Research Center for Regenerative Medicine. “This lays the foundation for future experiments in space, in which we will be able to include other parts of the brain affected by neurodegenerative diseases.”
On Earth, the team used stem cells to create organoids consisting of cortical or dopaminergic neurons, which are the neuronal populations affected by multiple sclerosis and Parkinson’s disease, diseases Loring has studied for decades. Some organoids also included microglia, a type of immune cell that resides within the brain, to examine the impact of microgravity on inflammation.
Organoids are typically grown in a nutrient-rich liquid medium that must be changed periodically to ensure the cells have adequate nutrition and remove waste products. To avoid the need for laboratory work on the ISS, the team pioneered a method to grow smaller-than-usual organoids in cryovials: small, airtight vials that were originally designed for deep freezing.
The organoids were prepared in laboratories on the Kennedy Space Station and traveled to the ISS in a miniature incubator. After a month in orbit, they returned to Earth, where the team proved they were healthy and intact.
To examine how the space environment affects cellular functions, the team compared the cells’ RNA expression patterns (a measure of genetic activity) with identical “Earth control” organoids that had remained on Earth. Surprisingly, they found that organoids grown in microgravity had higher levels of genes associated with maturity and lower levels of genes associated with proliferation compared to ground controls, meaning that cells exposed to microgravity developed faster. and they replicated less than those on Earth.
“We found that in both types of organoids, the gene expression profile was characteristic of an older developmental stage than those found on Earth,” says Loring. “In microgravity, they developed faster, but it’s really important to know that they weren’t adult neurons, so this doesn’t tell us anything about aging.”
The team also observed 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 reflect the conditions experienced by cells within the brain compared to organoids grown under conventional laboratory conditions and in the presence of gravity.
“The characteristics of microgravity probably also influence people’s brains, because in microgravity there is no convection; in other words, things don’t move,” says Loring. “I think that in space, these organoids are more like the brain because they don’t receive a lot of culture medium or oxygen. They are very independent; they form something like a brain, a microcosm of the brain.”
The article describes the team’s first space mission, but they have since sent four more missions to the ISS. With each one, they replicated the conditions of the first mission and added additional experiments.
“The next thing we plan to do is study the part of the brain most affected by Alzheimer’s disease,” Loring says. “We also want to know if there are differences in the way neurons connect to each other in space. With these types of studies, you can’t rely on previous work to predict what the outcome would be because there is no previous work. We are in the ground floor, so to speak; in heaven, but on the ground floor.”
This work was supported by funds from the National Stem Cell Foundation.