Researchers have used stem cell-derived neuronal organoids to study the effects of microgravity on the brain on the International Space Station (ISS). Neurons have been shown to develop more rapidly in space than on Earth, and future missions will seek to understand the causes. This is the first study of organoids associated with diseases such as multiple sclerosis and Parkinson’s on the ISS, with the aim of advancing neurodegenerative treatments.
Research on the International Space Station (ISS) seeks to understand how microgravity affects human health and explore its use to improve disease study and drug development. So far, studies have shown that microgravity alters muscles, bones, the immune system, and can influence balance and cognition.
Scientists at The New York Stem Cell Foundation Research Institute, USA, are studying how weightlessness on the International Space Station (ISS) affects the human body, especially the brain.
This is done to understand how these space conditions can impact our health and to explore new ways to treat diseases here on Earth.
They use models called organoids, which are tiny "mini-brains" created from human stem cells. These organoids are designed to mimic parts of the human brain, helping researchers study diseases like Parkinson's and multiple sclerosis.
The technique begins with the use of induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed to an embryonic-like state. These cells have the ability to transform into any type of cell in the body.
In the lab, the researchers directed these iPSCs to become specific neurons associated with the cerebral cortex and substantia nigra of the brain, areas affected by diseases such as multiple sclerosis and Parkinson’s.
These cells were then assembled into small, three-dimensional structures called organoids, which mimic basic aspects of the human brain.
To make the organoids more similar to the real brain, the scientists added microglia to some of them. Microglia are immune cells in the central nervous system that play a crucial role in defending the brain and regulating its health.
These cells were derived separately from the same iPSCs because they follow a different developmental process. The addition of microglia allowed the researchers to study the interactions between immune cells and neurons in microgravity conditions.
The organoids were grown in small tubes containing culture medium, a nutrient-rich liquid that keeps cells alive. This compact, sealed format was designed to avoid common problems in space, such as leaks caused by changes in gravity.
Each tube was carefully monitored for temperature and placed in special hardware for safe transport to the International Space Station (ISS). During the mission, the organoids remained in static culture, without nutrient exchange, for 30 days.
Experimental design. iPSCs from 4 individuals were selected for experiments: 2 controls and 2 with neurodegenerative diseases Parkinson’s disease or primary progressive multiple sclerosis. iPSCs were differentiated into cortical or dopaminergic neuron precursors, aggregated to form organoids, and matched microglia derived from each cell lineage were added to half of the organoids. Each organoid was placed in a separate cryovial with 1 mL of culture medium and sealed for the duration of the experiment. One set of cryovials was transported to the ISS on the SpX CRS-19 mission while the other replicate set remained on the ground. Matched sets of cryovial cultures were incubated for 1 month at 37 °C on the ground and on board the ISS. D. After return to Earth, both sets of organoid cultures were analyzed by various methods.
After the organoids returned from space, they were analyzed side by side with the samples cultured on Earth. Scientists examined their health, appearance, and cellular behavior using advanced methods such as immunocytochemistry to look for specific proteins, RNA sequencing to understand gene activity, and analysis of proteins secreted into the culture medium.
They found that the returned organoids were alive, extending long nerve connections called neurites, indicating neural maturation.
To confirm that the observed changes were caused by microgravity and not radiation, the researchers monitored radiation levels on the ISS during the mission.
The data showed that radiation exposure was minimal and comparable to that of astronauts, reinforcing that the absence of gravity was the main factor responsible for the differences observed between the space and ground organoids.
The results showed that the organoids grown in microgravity showed greater neural maturation, with genes related to cell proliferation being less expressed and genes associated with neural communication being more active.
Neural organoids cultured in the static system without medium exchange were viable after 30 days. A. Phase contrast images of cortical and dopaminergic neural organoids from pre-flight to post-flight stages in low Earth orbit (LEO) and on the ground. B. Organoids cultured after 30 days in LEO show neurite outgrowth with growth cones. C. Immunocytochemistry of cryosectioned cortical organoids shows the typical neural rosettes of cortical organoids (red: PAX6; green: CDH2 [NCAD]) for both ground and LEO samples. D. Telemetry shows the temperature maintained inside the CubeLab onboard the ISS and images show the organoid (arrows) cultured in the static system on mission days 5.119 and 30.09 (images taken onboard the ISS).
This accelerated maturation was accompanied by changes in Wnt signaling, a crucial mechanism for brain development. In addition, the space samples showed fewer signs of cellular stress than the Earth samples, which was an unexpected finding.
These results show that conditions in space can profoundly affect the functioning of brain cells. This helps scientists better understand how neurons work and how diseases that affect them can be treated.
In the future, these studies could contribute to the development of more effective drugs for conditions such as Parkinson’s and multiple sclerosis. In addition, this research helps prepare astronauts for long space missions, reducing the risk of brain problems caused by microgravity.
READ MORE:
Effects of microgravity on human iPSC-derived neural organoids on the International Space Station
Davide Marotta, Laraib Ijaz, Lilianne Barbar, Madhura Nijsure, Jason Stein, Nicolette Pirjanian, Ilya Kruglikov, Twyman Clements, Jana Stoudemire, Paula Grisanti, Scott A Noggle, Jeanne F Loring, Valentina Fossati
Stem Cells Translational Medicine, Volume 13, Issue 12, December 2024, Pages 1186–1197
Abstract:
Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson’s disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia. The organoids were cultured for a month using a novel sealed cryovial culture method on the International Space Station (ISS) and a parallel set that remained on Earth. Live samples were returned to Earth for analysis by RNA expression and histology and were attached to culture dishes to enable neurite outgrowth. Our results show that both cortical and dopaminergic organoids cultured in LEO had lower levels of genes associated with cell proliferation and higher levels of maturation-associated genes, suggesting that the cells matured more quickly in LEO. This study is continuing with several more missions in order to understand the mechanisms underlying accelerated maturation and to investigate other neurological diseases. Our goal is to make use of the opportunity to study neural cells in LEO to better understand and treat neurodegenerative disease on Earth and to help ameliorate potentially adverse neurological effects of space travel.
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