Brain cells mature faster in space, but stay healthy: ISS study

Microgravity is known to alter muscles, bones, the immune system, and cognition, but little is known about its specific effects on the brain. To understand how brain cells respond to microgravity, Scripps Research Institute scientists teamed up with the New York Stem Cell Foundation to send small clumps of stem cell-derived brain cells called “organoids” to the International Space Station. (ISS).

Surprisingly, when the organoids returned from orbit a month later, they were still healthy, but the cells had matured more quickly and resembled adult neurons compared to identical organoids grown on Earth. It was beginning to show signs of specialization. The results, which may shed light on the potential neurological effects of space travel, are published in Stem Cell Translational Medicine.

“The fact that these cells survived in space was a huge surprise,” said co-senior author Jeanne Loring, professor emeritus in the Department of Molecular Medicine and founding director of the Scripps Research Center for Regenerative Medicine. says the doctor. “This lays the foundation for future space experiments that can include other parts of the brain affected by neurodegenerative diseases.”

On Earth, the team used stem cells to create organoids composed of either cortical neurons or dopaminergic neurons. These are the neuronal populations affected by multiple sclerosis and Parkinson’s disease, which Rowling has been studying for decades. Some organoids also contained microglia, a type of immune cell found in the brain, to examine the effects of microgravity on inflammation.

Organoids typically grow in a nutrient-rich liquid medium that must be replaced regularly to provide adequate nutrition to the cells and remove waste products. To avoid the need for experimental work on the ISS, the research team developed a method to grow smaller-than-normal organoids in cryovials (small, airtight vials originally designed for deep freezing).

The organoids were prepared in a laboratory on the Kennedy Space Station and transported to the ISS in small incubators. After a month in orbit, they returned to Earth, where the team showed them to be healthy and unharmed.

To examine how the space environment affects cell function, the research team compared the cells’ RNA expression patterns, a measure of gene activity, with identical “ground control” organoids that remained on Earth. did. Surprisingly, we found that organoids grown in microgravity had higher levels of maturation-related genes and lower levels of proliferation-related genes compared to terrestrial controls. This means that cells exposed to microgravity develop faster and replicate less than cells on Earth.

“We found that in both types of organoids, the gene expression profiles were characteristic of older developmental stages than their terrestrial counterparts,” Loring says. “In the microgravity environment, they developed faster, but it’s very important to know that these are not adult neurons. So this doesn’t tell us anything about aging.”

The researchers also noted that, contrary to hypothesis, organoids grown in microgravity had reduced inflammation and reduced expression of stress-related genes, but further research is needed to understand why. .

Professor Loring speculates that microgravity conditions may more closely reflect the conditions experienced by cells in the brain compared to organoids grown under traditional laboratory conditions and in the presence of gravity. are.

“The properties of microgravity probably affect people’s brains, too, because there’s no convection in microgravity; in other words, things don’t move,” Rowling says. “In space, I think these organoids are more like brains because they’re not flushed out with a lot of medium or oxygen. They’re very independent, and they’re like brainlets, microcosms of the brain. is forming.”

This paper describes the team’s first space mission, but since then they have sent four more missions to the ISS. For each mission, we recreated the conditions of the first mission and added additional experiments.

“Our next plan is to study the parts of the brain that are most affected by Alzheimer’s disease,” Rowling says. “We also want to know if there are differences in the way neurons connect to each other in space. There are no previous studies of this type, so we can’t predict what the outcome will be. You can’t rely on previous research because you’re on the ground floor, so to speak.