Microgravity is known to affect muscles, bones, the immune system, and cognition, but its exact effects on the brain remain largely unexplored. To investigate how brain cells react to microgravity, researchers from Scripps Research, in partnership with the New York Stem Cell Foundation, dispatched small clusters of stem-cell derived brain cells known as “organoids” to the International Space Station (ISS).
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 tiny clumps of stem-cell derived brain cells called “organoids” to the International Space Station (ISS).
Upon their return from space after one month, the organoids remained healthy, but the cells had matured at a quicker pace than similar organoids grown on Earth. They were closer to resembling adult neurons and exhibited signs of specialization. These findings, which may reveal important insights into the neurological effects of space travel, were published on October 23, 2024, in Stem Cells Translational Medicine.
“It was a major surprise to see that these cells survived in space,” stated co-senior author Jeanne Loring, PhD, professor emeritus in the Department of Molecular Medicine and founding director of the Center for Regenerative Medicine at Scripps Research. “This sets the stage for future space experiments where we can include other brain areas impacted by neurodegenerative diseases.”
On Earth, the researchers created organoids that contained either cortical or dopaminergic neurons, which are affected in conditions like multiple sclerosis and Parkinson’s disease—illnesses that Loring has researched for many years. Some organoids also included microglia, a type of immune cell found in the brain, to assess the effects of microgravity on inflammation.
Typically, organoids grow in a nutrient-rich liquid medium that must be routinely updated to keep the cells nourished and to eliminate waste. To reduce the need for laboratory work on the ISS, the researchers developed a novel method to grow smaller organoids in cryovials—tiny, airtight containers originally intended for deep freezing.
The organoids were cultured at the Kennedy Space Center and were sent to the ISS in a compact incubator. After a month in orbit, they returned to Earth, where it was confirmed that they remained healthy and intact.
To study how the space environment influences cellular functions, the scientists compared the RNA expression patterns of the organoids—indicating gene activity—with their identical counterparts that stayed on Earth. Surprisingly, the microgravity-grown organoids showed higher levels of genes linked with maturity and lower levels tied to cell replication than their ground control counterparts, indicating that microgravity exposure promoted faster development and reduced replication.
“We found that in both types of organoids, the gene expression profiles indicated a more advanced stage of development than those on the ground,” Loring noted. “In microgravity, they matured faster, but it’s essential to emphasize that these were not adult neurons, so this does not provide insights into aging.”
Additionally, contrary to their expectations, the researchers observed reduced inflammation and lower expression of stress-related genes in the organoids developed in microgravity, though further studies are needed to understand these outcomes.
Loring speculates that the conditions of microgravity may replicate the environment that brain cells naturally experience more closely than organoids grown under standard laboratory conditions with gravity.
“Microgravity probably mimics some characteristics found in human brains, as there’s no convection,” she explained. “In essence, everything stays in place. I believe that in space, these organoids resemble the brain more because they aren’t subjected to a constant flow of nutrients or oxygen. They operate independently; it’s like forming a brainlet, a small-scale model of the brain.”
This study marks the first mission undertaken by the team; since then, they have conducted four additional missions to the ISS. Each subsequent mission has repeated the initial conditions while incorporating extra experiments.
“Our next objective is to investigate the brain region most affected by Alzheimer’s disease,” says Loring. “We also want to determine if there are differences in how neurons connect with one another in space. With this type of research, we can’t predict results based on past studies since there’s no prior work to reference. We are, quite literally, at the beginning stages; in the sky, yet on the ground floor.”
This research was funded by the National Stem Cell Foundation.
