Low gravity in space travel weakens and disrupts the normal rhythm of heart muscle cells

Scientists from Johns Hopkins Medicine who arranged for 48 genetically engineered human heart tissue samples to stay on the International Space Station for 30 days report that the low-gravity conditions in space weakened the tissues and disrupted their normal rhythmic beating compared to Earth-based samples from the same source.

Scientists said heart tissue “doesn’t do very well in space” and that over time, tissue on the space station beats about half as hard as tissue from the same source stored on Earth.

These findings, they say, expand scientists’ knowledge of the potential effects of low gravity on astronaut survival and health during long space missions, and they could serve as models for studying heart muscle aging and therapies on Earth.

A report on the scientists’ tissue analysis is published in the Proceedings of the National Academy of Sciences.

Previous studies have shown that some astronauts return to Earth from space with age-related problems, including reduced heart muscle function and arrhythmias (irregular heartbeats), and that some, but not all, effects dissipate over time after their return.

But scientists have been looking for ways to study these effects at the cellular and molecular level to find ways to protect astronauts during long spaceflights, says Deok-Ho Kim, Ph.D., professor of biomedical engineering and medicine at the Johns Hopkins University School of Medicine. Kim led the project to send heart tissue to the space station.

To create the cardiac payload, scientist Jonathan Tsui, Ph.D., coaxed human induced pluripotent stem cells (iPSCs) to develop into heart muscle cells (cardiomyocytes). Tsui, who was a doctoral student in Kim’s lab at the University of Washington, accompanied Kim as a postdoctoral researcher when Kim moved to Johns Hopkins in 2019. They continued the space biology research at Johns Hopkins.

Tsui then placed the tissues in a miniaturized, bioengineered tissue chip that threads the tissues between two posts to collect data on how the tissues beat (contract). The 3D casing of cells was designed to mimic the environment of an adult human heart in a chamber half the size of a cell phone.

To get the tissues to the space station on SpaceX’s CRS-20 mission, which launched in March 2020, Tsui said he had to hand-carry the tissue chambers on a plane to Florida and continue caring for the tissues for a month at Kennedy Space Center. Tsui is now a scientist at Tenaya Therapeutics, a company that specializes in preventing and treating heart disease.

Once the tissues were on board the space station, scientists received real-time data for 10 seconds every 30 minutes on how hard the cells were contracting, called twitch force, and any irregular beating rhythms. Astronaut Jessica Meir, Ph.D., MS, changed the liquid nutrients surrounding the tissues once a week and stored the tissues at specific intervals for later gene readings and imaging analyses.

The research team kept a set of heart tissues grown in the same way on Earth, housed in the same type of chamber, to compare them with the tissues present in space.

When the tissue chambers returned to Earth, Tsui continued to maintain and collect data on the tissues.

“An incredible amount of cutting-edge technology in stem cell and tissue engineering, biosensors and bioelectronics, and microfabrication has been used to ensure the viability of these tissues in space,” says Kim, whose team developed the tissue chip for this and subsequent projects.

Devin Mair, Ph.D., a former doctoral student in Kim’s lab and now a postdoctoral researcher at Johns Hopkins, then analyzed the tissues’ ability to contract.

In addition to losing strength, heart muscle tissue in space developed irregular beats (arrhythmias), disturbances that can cause the human heart to fail. Normally, the time between heartbeats in heart tissue is about one second. In the tissue on the space station, that time became nearly five times longer than in Earth tissue, although the time between beats returned to near normal when the tissue returned to Earth.

Scientists also found that in the tissues sent into space, sarcomeres (the protein bundles in muscle cells that help them contract) became shorter and more disordered, a hallmark of human heart disease.

Additionally, the energy-producing mitochondria in the space-bound cells became larger, rounder, and lost the characteristic folds that help cells use and produce energy.

Finally, Mair, Eun Hyun Ahn, Ph.D., research assistant professor of biomedical engineering, and Zhipeng Dong, a doctoral student at Johns Hopkins, studied gene readouts in tissues preserved in space and on Earth. The space station tissues showed increased production of genes involved in inflammation and oxidative damage, also hallmarks of heart disease.

“Many of these markers of oxidative damage and inflammation are routinely highlighted during post-flight checks of astronauts,” Mair says.

Kim’s lab sent a second batch of 3D-created heart tissue to the space station in 2023 to look for drugs that could protect cells from the effects of low gravity. That study is ongoing, and scientists say those same drugs could help people maintain their heart function as they age.

Scientists continue to improve their “tissue-on-a-chip” system and study the effects of radiation on heart tissue at NASA’s Space Radiation Laboratory. The space station is in low orbit around Earth, where the planet’s magnetic field shields its occupants from most of the effects of space radiation.