Space Experiment Reveals Surprising Brain Cell Behavior

Though little is known about the precise effects of microgravity on the brain, it is known to change the immune system, muscles, bones, and cognition. Scientists from Scripps Research, working with the New York Stem Cell Foundation, sent small clusters of brain cells derived from stem cells, known as “organoids,” to the ISS to learn how brain cells react to microgravity.

When they returned from orbit a month later, the organoids were surprisingly still healthy, but the cells had developed more quickly than those of identical organoids grown on Earth; they were starting to show signs of specialization and were getting closer to becoming adult neurons.

The findings, published in the journal Stem Cells Translational Medicine, help clarify possible neurological impacts of space travel.

The fact that these cells survived in space was a big surprise. 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.”

Jeanne Loring, PhD, Professor Emeritus, Study Co-Senior Author and Founding Director, Center for Regenerative Medicine, Scripps Research

The organoids created by the team on Earth using stem cells were modeled after cortical and dopaminergic neurons, the neuronal populations affected in multiple sclerosis and Parkinson’s disease, which Loring has studied extensively for decades. To investigate the effect of microgravity on inflammation, some organoids also contained microglia, a subset of immune cells found in the brain.

Organoids are typically cultivated in a nutrient-rich liquid medium that needs to be changed frequently to guarantee that the cells receive enough nourishment and eliminate waste. The team developed a technique for cultivating smaller-than-normal organoids in cryovials, tiny, airtight vials initially intended for deep freezing, to circumvent the need for laboratory work on the ISS.

The organoids were transported to the ISS in a tiny incubator after being prepared in labs at the Kennedy Space Station. When they returned to Earth after a month in orbit, the crew demonstrated that they were unharmed.

The team compared the cells’ RNA expression patterns, a measure of gene activity, to identical “ground control” organoids that had stayed on Earth to investigate how the space environment affects cellular functions.

In contrast to the ground controls, they discovered that the organoids grown in microgravity exhibited lower levels of genes linked to proliferation and higher levels of genes linked to maturity. This suggests that the cells exposed to microgravity developed more quickly and replicated less than those grown 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 the ground. In microgravity, they developed faster, but it is really important to know these were not adult neurons, so this does not tell us anything about aging.”

Jeanne Loring, PhD, Professor Emeritus, Study Co-Senior Author and Founding Director, Center for Regenerative Medicine, Scripps Research

In addition, the team observed that, in contrast to their prediction, organoids grown in microgravity showed reduced inflammation and reduced expression of genes linked to stress; however, further investigation is required to ascertain the reason for this.

In contrast to organoids cultivated in the presence of gravity and under standard laboratory conditions, Loring hypothesizes that microgravity conditions might more closely resemble those that cells in the brain encounter.

The characteristics of microgravity are probably also at work in people's brains, because there is no convection in microgravity in other words, things do not move. I think that in space, these organoids are more like the brain because they are not getting flushed with a whole bunch of culture medium or oxygen. They are very independent; they form something like a brainlet, a microcosm of the brain.”

Jeanne Loring, PhD, Professor Emeritus, Study Co-Senior Author and Founding Director, Center for Regenerative Medicine, Scripps Research

The team has sent four more missions to the ISS since their first space mission, which is described in the paper. They have added more experiments and reproduced the conditions from the first mission with each one.

Loring concluded, “The next thing we plan to do is to study the part of the brain that is most affected by Alzheimer's disease. 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 cannot rely on earlier work to predict what the result would be because there is no earlier work. We are on the ground floor, so to speak; in the sky, but on the ground floor.”