As part of the Cerebral Ageing experiment, 84 brain organoids were grown for over a month on the International Space Station. A real challenge and a world first!
After a 40-day stay aboard the International Space Station (ISS), the brain organoids returned to Earth in late December 2023. These lab-grown human brain structures are the first organoids ever to be grown in space – some had only previously been there.” They came back alive and in very good health ,” explains Frank Yates , a teacher-researcher at SupBiotech. “We are very happy with this mission, which is a real success. “
This experiment, called Cerebral Aging, demonstrates for the first time that it is possible to grow brain organoids in space.
This is a paradigm shift for scientific research in this field! Miria Ricchetti, head of the Molecular Mechanisms of Pathological and Physiological Aging group at the Pasteur Institute.
Initiated in 2019, Cerebral Ageing is a cell biology experiment developed by CADMOS at CNES (see box below), the Pasteur Institute , SupBiotech and BioServe.
Its objective? To establish a model to study brain aging on a very small scale, that of the cell and even the molecule. The analysis of these structures allows scientists to better understand what happens in an aging brain.
” Many experiments are conducted on samples – blood for example – from astronauts ,” explains Miria Ricchetti. However, it is impossible to study a piece of human brain, which is why we use cerebral organoids that mimic the structure and composition of a developing brain. “
Miniature brain structures derived from human cells
The recipe for a brain organoid? In the laboratory (” in vitro “), scientists use human stem cells. These undifferentiated cells have the ability to differentiate into almost any cell in the human body. All they need to do is cultivate them in a very specific medium for them to differentiate into cardiac cells, muscle cells, etc. or several neural cells (i.e. those that make up a human brain or an organoid) in the case of Cerebral Ageing.
Once they have multiplied sufficiently, differentiated into several cell types and structured into well-defined layers, they form an organoid. ” These are 3D structures made up of different types of structured and interacting cells, like a developing human brain ,” adds Miria Ricchetti. For Cerebral Ageing, scientists have made several hundred brain organoids, 84 of which have been sent to the ISS.
Space is a very interesting environment for scientists to study: microgravity and cosmic radiation influence living organisms. ” Our hypothesis is that these conditions accelerate aging ,” adds Frank Yates. ” We are among the first to send organoids that have been cultured for so long! ” The Cerebral Ageing experiment therefore aims to demonstrate the possibility of sending and cultivating in space, then recovering, living or immobilized cerebral organoids.
The ISS provides a unique environment to carry out this experiment: in orbit at an altitude of 400 km, it has been dedicated to carrying out scientific experiments in microgravity since 1998.
A look back at the organoids’ stay on board the ISS
Growing organoids in space is a path fraught with pitfalls… all of which the team overcame. “ We know perfectly well how to grow them in our laboratories, but the conditions for carrying out the experiment on the ISS were new to us, requiring us to do real biotechnological engineering work ,” says Frank Yates. Didier Chaput, head of life sciences experiments at CADMOS (CNES), adds: “ Our role was to support the scientific teams from the early stages of the project to carry it out in space conditions. This allows them to focus solely on science.” With the Bioserve team, CNES ensured that all the equipment needed for the experiment was present on board the ISS.
Step One: Build the Brain Organoids and Ensure the Feasibility of the Experiment
” Working for the ISS requires optimizing the resources allocated to the experiment to the maximum to reduce costs, such as the volume and the astronaut time dedicated to carrying out operations during the flight ,” explains Didier Chaput. On the ground, organoids measuring a few millimeters were produced and cultivated in specially designed cassettes supplied by the American company Bioserve. These initial tests, which were successfully completed, validated the feasibility of the experiment on the ground in conditions as close as possible to those of the flight, paving the way to the ISS.
Step two: transporting the organoids to the ISS
384 organoids were placed in two hermetically sealed containers, ensuring a constant temperature of 37°C and a CO2 level of 5%. These conditions are essential to keep the organoids alive. The two incubators were taken to the Kennedy Space Center at Cape Canaveral in Florida. After careful selection, 84 organoids were placed in the 14 flight cassettes with culture medium and then delivered to NASA a few hours before their departure aboard the Falcon 9 rocket on November 9, 2023. The unselected organoids continued their development on the ground, serving as control samples.
Step 3: Carry out the scientific experiment on board the ISS
It was one of the most important and difficult. Three astronauts conducted the experiment on board the ISS: Lora O’Hara (NASA), Jasmin Moghbeli (NASA) and Andreas Mogensen (ESA).
” To survive, organoids need to be fed: their culture medium must be renewed ,” explains Frank Yates. ” For the first time, we have made this possible for brain organoids, while minimizing the frequency of renewal of the medium because the astronauts’ time on board is precious. “
The cassettes have a slot where a syringe filled with fresh culture medium can be inserted by the astronaut. Another syringe is used to aspirate the used culture medium. Finally, the astronauts followed a precise scientific protocol. At 3 times (2 days after arrival on board, in the middle of the mission and before returning to Earth), some organoids were immobilized. ” They are either frozen or “fixed” by a specific product ,” explains Miria Ricchetti. This makes it possible to analyze their condition at the time of immobilization, and thus review their evolution over time .”
Step Four: Bringing the Organoids Back to Earth
As planned, the 12 still living organoids were brought back under the same conditions as on the way there. As for the fixed ones, they were in refrigerated containers at 4°C or -80°C.
“Returning the living organoids to the scientists was a real relief, a sign of the success of the mission despite the many unforeseen events we had to face. Thanks to the rigorous protocol followed, the results of this experiment are robust and will help advance scientific knowledge, according to Didier Chaput, head of life sciences experiments at CADMOS at CNES.
Astronaut Health and Alzheimer’s Disease
Scientists are now working on the final stage of the project: analyzing all the samples repatriated to France since February 2024. Three types of measurements are being carried out. The organoids are cut into thin slices and observed under a microscope in order to detail the state and composition of the cells. Genetic analyses will also be carried out using modern and recent tools. Finally, the used culture medium has also been brought back to Earth: ” the molecules released by the organoids – called metabolites – tell us about their state of health ,” explains Miria Ricchetti. And to deduce the consequences of their stay in space, the scientists have another trick up their sleeve: ” We cultivated other brain organoids on Earth at the same time, which will serve as controls. “
The organoids will reveal their first secrets by the end of 2024. These results will notably make it possible to begin exploring the effects of stays in space on avatars of astronauts’ brains, an essential prerequisite for the future of space exploration and the protection of astronauts during long-duration missions.
If it turns out that aging is accelerated in space, growing brain organoids opens the door to exciting research for teams working on degenerative diseases like Alzheimer’s, says Frank Yates, teacher-researcher at SupBiotech
By observing molecular and cellular changes in an aging organoid, scientists will better understand the development of degenerative pathologies. Brain organoids have not finished making headlines.