Researchers from Johns Hopkins Medicine have reported findings from an experiment involving 48 human bioengineered heart tissue samples sent to the International Space Station (ISS) for 30 days. The results indicate that the low-gravity environment in space weakened the heart tissues and disrupted their typical rhythmic contractions compared to similar samples kept on Earth.
Researchers from Johns Hopkins Medicine have reported findings from an experiment involving 48 human bioengineered heart tissue samples sent to the International Space Station (ISS) for 30 days. The results indicate that the low-gravity environment in space weakened the heart tissues and disrupted their typical rhythmic contractions compared to similar samples kept on Earth.
The researchers noted that the heart tissues “really don’t fare well in space,” revealing that over time, the contractions performed by the tissues on the ISS were roughly half as powerful as those from the Earth-based samples.
These findings broaden the understanding of the potential impacts that low gravity can have on the survival and well-being of astronauts during extended space missions, and they might also provide important models for researching heart muscle aging and potential treatments on Earth.
A detailed report on the tissue analysis will be made public during the week of September 23 in the journal Proceedings of the National Academy of Sciences.
Earlier studies have found that some astronauts return to Earth experiencing age-related issues, such as diminished heart muscle function and arrhythmias (irregular heartbeats), with some effects gradually alleviating after their return.
Researchers have been investigating these effects at a cellular and molecular level to discover ways to ensure astronauts’ health during long-duration space flights, as explained by Deok-Ho Kim, Ph.D., a professor of biomedical engineering and medicine at the Johns Hopkins University School of Medicine. Kim was the leader of the project that sent the heart tissues to the space station.
To prepare the cardiac samples, scientist Jonathan Tsui, Ph.D., guided human induced pluripotent stem cells (iPSCs) to transform into heart muscle cells known as cardiomyocytes. Tsui had been a Ph.D. student in Kim’s lab at the University of Washington and joined Kim as a postdoctoral fellow when Kim transitioned to Johns Hopkins University in 2019, continuing their research into space biology.
Tsui encapsulated the tissues in a miniature bioengineered tissue chip that stretches the tissues between two posts, allowing them to gather data regarding their contraction behavior. This three-dimensional housing was designed to imitate the conditions of a human heart, fitting into a chamber about half the size of a mobile phone.
In order to transport the tissue samples aboard the SpaceX CRS-20 mission—launched in March 2020 for the ISS—Tsui had to personally carry the tissue chambers on a flight to Florida and maintain care for them for a month during their stay at the Kennedy Space Center. Tsui now works as a scientist at Tenaya Therapeutics, a company dedicated to heart disease prevention and treatment.
Once the tissues arrived on the space station, the scientists received data every 30 minutes for 10 seconds regarding the strength of tissue contractions, termed twitch forces, as well as any irregularities in their beating patterns. Astronaut Jessica Meir, Ph.D., M.S., changed the nutrient liquid surrounding the tissues weekly and preserved samples at set times for subsequent gene expression and imaging evaluations.
The research team also maintained a set of cardiac tissues developed in the exact manner on Earth for comparison with those in space.
After the tissue chambers returned to Earth, Tsui continued to take care of and analyze the tissues.
“An incredible amount of cutting-edge technology in stem cell and tissue engineering, biosensors, and microfabrication was essential for ensuring the viability of these tissues in space,” states Kim, whose team developed the tissue chip for this and future projects.
Devin Mair, Ph.D., a past Ph.D. student in Kim’s lab who is now a postdoctoral fellow at Johns Hopkins, later examined how well the tissues could contract.
Along with the decrease in strength, the heart muscle tissues in space also displayed irregular beating (arrhythmias)—disruptions that could lead to heart failure. Typically, the interval between a cardiac tissue’s beats is around one second. For the tissues aboard the ISS, this interval extended to nearly five times longer than their Earth counterparts, although it returned to almost normal levels once the tissues came back to Earth.
Furthermore, the researchers observed that the sarcomeres—protein structures in muscle cells responsible for contraction—shortened and became disordered in the tissues that traveled to space, which is a sign of heart disease in humans.
Additionally, the mitochondria, which generate energy in the space-bound cells, enlarged, became rounder, and lost the crucial folds that aid in energy utilization and production.
Lastly, Mair, along with Eun Hyun Ahn, Ph.D., an assistant research professor of biomedical engineering, and Zhipeng Dong, a Johns Hopkins Ph.D. student, examined the gene activity in the tissues both in space and on Earth. The samples from the ISS exhibited heightened gene expression related to inflammation and oxidative damage, both of which are indicative of heart disease.
“Many of these signs of oxidative damage and inflammation have been consistently observed in post-flight assessments of astronauts,” Mair explains.
Kim’s lab has sent a second batch of 3D engineered heart tissues to the ISS in 2023 to explore drugs that might protect these cells against low gravity effects. This research is ongoing, and according to the scientists, the same medications could help individuals maintain heart function as they age.
The researchers continue to enhance their “tissue on a chip” system and are examining the influence of radiation on heart tissues at the NASA Space Radiation Laboratory. Notably, the ISS is located in low Earth orbit, where the Earth’s magnetic field provides protection from most forms of space radiation.
Kim is a co-founder, a member of the scientific advisory board, and an equity holder of Curi Bio, a company that focuses on developing bioengineered tissue platforms for drug development. Ahn, who is Kim’s spouse, serves as a co-investigator or principal investigator on multiple NIH grants: UG3EB028094, UH3TR003519, and R21CA220111.
Funding for this research was granted by the National Institutes of Health (UG3EB028094, UH3TR003519, UH3TR003271, R01HL164936, R01HL156947, R21CA220111).
