As Flights End, Tissue Chips in Space Projects Offer Glimpses Into the Biology of Aging

International Space Station U.S. National Lab’s Expedition 59 crew member Christina Koch assists with the University of Washington’s and UW Medicine’s kidney tissue chips in space. (NASA)

March 23, 2023

More than five years into the NCATS-led Tissue Chips in Space program, the final two projects arrived at the International Space Station National Laboratory (ISS National Lab) on March 16, 2023, after a successful launch from the Kennedy Space Center. This is their second and final trip to the ISS National Lab.

These final two projects from Stanford University and Johns Hopkins Medicine are examining different aspects of heart function and disease development and the effects of drugs in preventing changes to heart tissue and cells.

Tiny Technology, Faster Findings

Tissue chips are tiny, bioengineered packages of cells and tissues that can mimic the function of tissues and organs, as well as their environment inside the body. Tissue chips on the ISS National Lab provide a unique opportunity for researchers to model and study conditions related to diseases and aging that mimic what happens to astronauts in the microgravity environment of space. The Tissue Chips in Space projects seek to model these changes — which are like the effects seen in aging — over weeks, rather than the years that it would take for these conditions to occur on Earth.

Over the years, nine projects have gone to space. They have studied the aging of the immune system, muscle wasting, injury-related osteoarthritis, age-related changes in kidney function, respiratory system immune defenses, the blood–brain barrier, and the intestines and infection.

“The Tissue Chips in Space program showed we could do sophisticated experiments in space and advance translational science,” said Danilo Tagle, Ph.D., director of the NCATS Office of Special Initiatives, which oversees the umbrella Tissue Chip for Drug Screening program. “We’ve pioneered viable long-term science in space, including personalized approaches to therapeutics involving differences in diverse populations’ physiological responses.”

The partnership with the National Aeronautics and Space Administration (NASA) and the ISS National Lab was crucial to the program’s success, Tagle said. NASA views tissue chips as a valuable tool for studying astronauts’ physiological responses in space in greater depth.

“But more importantly, the lessons learned from these out-of-this-world experiments are geared toward translation of technologies and mitigation of aging effects on Earth,” he said.

When the program began in 2017, the initial goal “was just to find out if we could run a tissue chip experiment in low-gravity conditions in space,” Tagle said. Funded researchers needed to show if tissue chips could survive launches, function in microgravity and be able to capture biological markers and hallmarks of the more rapid aging seen in astronauts.

Once the initial tissue chips experiments proved possible in space, scientists wanted to identify the molecular changes that caused cells and tissues to mimic the aging process. They tested compounds and drugs to see if they could slow down or prevent aging effects and translate the results into treatments that help people on Earth.

The circumstances of spaceflight forced scientists and engineers to innovate. Experiments had to be automated and “astronaut-proof” to lessen the amount of crew time needed to conduct experiments. Engineers had to miniaturize the instrumentation needed to sustain the chips so they fit the payload requirements for both the SpaceX rockets and operations within the ISS National Lab. Scientific teams had to be flexible and deal with changing experiment conditions, challenges in transporting often-fragile cells and tissues, and changing launch schedules.

“We had to be creative in how we designed our experiments and be able to adapt and react quickly to problems when they invariably came up,” said Sonja Schrepfer, M.D., Ph.D., a project principal investigator at the University of California, San Francisco.

Schrepfer’s team is using tissue chip technology to better understand how a person’s aging immune system can affect how the body heals injured tissue. Her initial experiment was the first NIH-funded tissue chip project to go into orbit.

“We can use space and microgravity to induce the immune cells to age rapidly. There’s no other system to do this in,” she explained. “The chips provide a unique opportunity to examine cells in a more human-like physiological environment.”

Schrepfer and colleagues think that certain immune cells are tied to the ability of stem cells to regenerate tissue and heal injuries and wounds. Their first space experiments revealed that spaceflight hindered stem cells’ abilities to repair damaged tissue. Since the project’s second flight last year, the scientists have been analyzing the cellular changes. They hope their results will offer opportunities to stop or slow down the aging of immune cells.

For Massachusetts Institute of Technology (MIT) biological engineering professor Alan Grodzinsky, Sc.D., low-Earth orbit is a chance to learn more about preventing joint injuries in kids and young adults from developing into osteoarthritis later in life. The MIT tissue chip uses a matrix of human cartilage, bone and the surrounding synovial tissue that creates joint-lubricating fluid to test potential osteoarthritis-preventing treatments.

“We want to know what happens years later to the 14-year-old girl who tears her ACL playing soccer,” Grodzinsky said. “When the injury occurs, there’s physical damage and an inflammatory reaction in the knee. It sets the stage for a process that can lead to long-term osteoarthritis. We tried to simulate that process and see if drugs could slow it down.”

The Next Frontier

The March 2023 spaceflight will not be the final word from the Tissue Chips in Space program. NCATS plans to issue a funding opportunity aimed at translating what scientists and engineers have learned from the program to improve the use of tissue chips on Earth in terms of automation and miniaturization of the platform instruments.

“The goal is to make tissue chip technologies easier to use as turn-key technologies. Companies won’t need to invest in specialized expertise to run platforms,” said Tagle.

The Tissue Chips in Space teams will continue to study the results and publish their findings in journals. In the meantime, Tagle and NCATS will work with NASA to test the use of long-term tissue chips. Most of the tissue chip experiments on the ISS National Lab run about a month. They want to see if tissue chips that last as long as six months can help scientists understand what might happen to humans during long spaceflights to Mars. On Earth, researchers hope such tissue chips can model how chronic exposure to radiation, hazardous environments or drugs can affect human health.