It's no secret that prolonged time in space takes a toll on the human body. For years, NASA and other space agencies have been studying the effects of microgravity on humans, animals, and plants aboard the International Space Station (ISS). So far, research has shown that prolonged time in space leads to muscle atrophy, bone loss, changes in vision, gene expression, and mental health issues. Given our future goals in space exploration, which include long-term missions to the Moon, Mars, and beyond, it's critical to understand these effects and how to mitigate them.
However, a recent experiment conducted by researchers at Johns Hopkins University and supported by NASA's Johnson Space Center shows that heart tissues “really don't fare well” in space. The experiment involved 48 samples of human bioengineered heart tissue that were sent to the ISS for 30 days. As they state in their article, the experiment shows that microgravity weakens heart tissue and impairs its ability to maintain rhythmic beats. These results show that additional measures need to be taken to ensure that people can maintain their cardiovascular health in space.
The study was led by Deok-Ho Kim and colleagues from the Johns Hopkins University Department of Biomedical Engineering (BME-JHU) and the JHU Center for Microphysiology Systems. They were joined by researchers from UC Boulder's Ann and HJ Smead Department of Aerospace Engineering Sciences, the University of Washington's Institute for Stem Cell & Regenerative Medicine (ISCRM) and Center for Cardiovascular Biology, the Stanford Institute for Stem Cell & Regenerative Medicine, BioServe Space Technologies, and NASA's Johnson Space Center. The paper detailing their findings was published yesterday (Sept. 23) in the Proceedings of the National Academy of Sciences.
Heart tissue in one of the chambers ready for launch. Photo credit: Jonathan Tsui
Previous research has shown that astronauts returning to Earth from the ISS suffer a variety of health effects associated with certain age-related conditions, including reduced heart muscle function and irregular heartbeats (arrhythmias), most of which disappear over time. However, none of these studies have looked at what happens at the cellular and molecular level. To learn more about these effects and how to mitigate them, Kim and his colleagues sent an automated “heart-on-a-chip” platform to the ISS to study them.
To create this payload, the team used human induced pluripotent stem cells (iPSCs), which can transform into many cell types, to produce cardiomyocytes (heart muscle cells). These resulting tissues were placed into a miniaturized bioengineered tissue chip designed to mimic the environment of an adult human heart. The chips would then collect data on how the tissues would rhythmically contract, mimicking the heartbeat. One set of biochips was carried to the ISS aboard the SpaceX CRS-20 mission in March 2020, while another remained on Earth as a control group.
On the ISS, astronaut Jessica Meir took care of the experiment. She changed the liquid nutrients around the tissues once a week and preserved the tissue samples at certain intervals so that genetic and image analysis could be carried out upon their return to Earth. In the meantime, the experiment sent real-time data on the contractions and irregular heartbeat patterns (arrhythmias) of the tissue samples to Earth every 30 minutes (for 10 seconds each).
“An incredible amount of cutting-edge technology in stem cell and tissue engineering, biosensors and bioelectronics, and microfabrication has been deployed to ensure the viability of these tissues in space,” Kim said in a recent Hub press release.
When the tissue chambers returned to Earth, he and his colleagues continued to carry the samples and collect data to see if their ability to contract changed. In addition to losing strength, the muscle tissues developed arrhythmias consistent with age-related heart disease. In a healthy human heart, the time between beats is about one second, while the tissue samples lasted nearly five times as long — although they returned almost to normal after returning to Earth.
The team also found that the tissue cells' protein bundles that help them contract (sarcomeres) were shorter and more disorganized than those of the control group, another symptom of heart disease. In addition, mitochondria in the tissue samples became larger and rounder, losing the characteristic folds that help them produce and use energy. Finally, gene reading in the tissues showed increased gene production related to inflammation and an imbalance of free radicals and antioxidants (oxidative stress).
Not only is this consistent with age-related heart disease, but it has been demonstrated again and again in the astronauts' post-flight examinations. The team says these findings expand our scientific knowledge of the potential effects of microgravity on human health in space, and could also advance research into heart muscle aging and therapy on Earth. In 2023, Kim's lab continued this experiment by sending a second batch of tissue samples to the ISS to test drugs that could help protect heart muscle from the effects of microgravity and help people maintain their heart function as they age.
In the meantime, the team continues to improve its tissue-on-a-chip system and has partnered with NASA's Space Radiation Laboratory to study the effects of space radiation on heart muscle. These tests will assess the threat that solar and cosmic radiation pose to cardiovascular health beyond low Earth orbit (LEO), where Earth's magnetic field protects against the greatest amount of space radiation.
Further reading: John Hopkins University, PNAS
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