Microgravity is known to
alter the 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).
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 potential neurological effects of space
travel, were published on October 23, 2024, in Stem
Cells Translational Medicine.
“The fact that these cells survived in
space was a big surprise,” says 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 lays the groundwork
for future experiments in space, in which we can include other parts of the
brain that are affected by neurodegenerative disease.”
On Earth, 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—diseases that Loring has studied for decades. Some organoids also
included microglia, a type of immune cell that is resident within the brain, to
examine the impact of microgravity on inflammation.
Organoids are usually grown in a
nutrient-rich liquid medium that must be changed regularly to ensure that the
cells have adequate nutrition, and to remove waste products. To avoid the need
for lab work on the ISS, the team pioneered a method for growing
smaller-than-usual organoids in cryovials—small, airtight vials that were
originally designed for deep freezing.
The organoids were prepared in labs at
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 showed that they
were healthy and intact.
To examine how the space environment
impacts cellular functions, the team compared the cells’ RNA expression
patterns—a measure of gene activity—to identical “ground control” organoids
that had remained on Earth. Surprisingly, they found that the organoids grown
in microgravity had higher levels of genes associated with maturity and lower
levels of genes associated with proliferation compared to the ground controls,
meaning that the cells exposed to microgravity developed faster and replicated
less than those on Earth.
“We discovered that in both types of
organoids, the gene expression profile was characteristic of an older stage of
development than the ones that were on ground,” says Loring. “In microgravity,
they developed faster, but it’s really important to know these were not adult
neurons, so this doesn’t tell us anything about aging.”
The team also noted that, contrary to
their hypothesis, there was less inflammation and lower expression of
stress-related genes in 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 to organoids grown under conventional lab conditions and in
the presence of gravity.
“The characteristics of microgravity are
probably also at work in people’s brains, because there’s no convection in
microgravity—in other words, things don’t move,” says 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 describes the team’s first
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,”
says Loring. “We also want to know whether there are differences in the way
neurons connect with each other in space. With these kinds of studies, you
can’t rely on earlier work to predict what the result would be because there is
no earlier work. We’re on the ground floor, so to speak; in the sky, but on the
ground floor.”
Source: https://www.scripps.edu/news-and-events/press-room/2024/20241216-loring-stem-cells.html
Journal article: https://academic.oup.com/stcltm/article/13/12/1186/7833382
Image: Brain organoids were healthy and continued to grow after spending a month on the International Space Station. (Credit: Jeanne Loring
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