Space is a long way to go to learn about human tissues, yet researchers have their gazes trained at the stars.
Earlier this year, a team of researchers from the University of Zurich (UZH) sent 250 test tubes of carefully prepped human stem cells to the U.S. National Laboratory on the International Space Station (ISS). They wanted to study how the near-weightless, microgravitational environment of the ISS affects these building-block cells in the hope of understanding some of the secrets of how they grow, divide and form into tissues.
Stem cells are special “generic” cells that have the potential to evolve into specialized ones, such as those that form muscle, blood, brain and other tissues. They can also divide and renew themselves. Researchers say this makes them invaluable as a potential backup resource to repair the body in case of damage from illness or injury.
Stem-cell-based therapies have begun to be used in cancers, heart conditions, neurological diseases, liver cirrhosis, arthritis and spinal cord injuries. Scientists are even considering stem-cell-based therapies for the treatment of covid-19, and are testing these in the lab.
Human stem cells come from different sources, including embryonic tissue (discarded embryos, cord blood or amniotic fluid) and nonembryonic tissue (present in organs and tissues of human bodies). There are still plenty of unknowns about these cells – such as, how they differentiate into other kinds of cells, or how they divide and repair themselves.
Scientists hope that studying the properties in low Earth orbit (up to 1,200 miles from the planet’s surface) might help answer some of these questions. This will, in turn, guide researchers working to develop better stem cell therapies and also potentially help them test drugs on human cells without needing to conduct experiments on animals.
“Weightlessness creates a completely different . . . environment that has fundamental effects on biological processes,” says Oliver Ullrich, director of the UZH Space Hub and chair of Anatomy/Gravitational Biology and Cell Biomechanics. “On the ISS, we succeeded in producing significantly larger . . . differentiated tissue from human stem cells [than we could on Earth] . . . We do not know why stem cells differentiate so excellently . . . in weightlessness. Basic research will one day be able to answer this question.”
Until then, he says, the goal is to develop biotechnologies that can help humans on Earth.
Some of the mysteries of stem cells might emerge from another space effort, a collaboration between the University of California at San Diego’s Sanford Stem Cell Clinical Center and Space Tango, a Lexington, Ky.-based engineering company manufacturing specialized automated platforms that allow scientists to carry out health and technology research in space.
In April, NASA awarded a $5 million grant to UCSD and Space Tango to develop a new lab called the Integrated Space Stem Cell Orbital Research (ISSCOR, pronounced “I score”) on ISS, and launch a bunch of stem cell experiments next year.
Catriona Jamieson, deputy director of the Moores Cancer Center at UCSD, is one of the participants in the collaboration. Her project looks at how cells turn cancerous as they age, the ways cancer begins in people and the breakdown of the human body’s immune system.
Sometimes, she says, mutations in our bone marrow stem cells give rise to precancerous cells that can lead to leukemia. On Earth, under the protection of the ozone layer that keeps out ultraviolet radiation from the sun, this process of good cells turning cancerous can take decades. In space, on the other side of the ozone layer, blood-forming stem cells are exposed to the sun’s UV radiation, causing them to become precancerous much faster.
This accelerated time frame allows her team to study how healthy blood cells become malignant without needing to wait for years to replicate the process on Earth.
Cell cultures in a lab on Earth grow in a single layer – think of it as a two-dimensional structure – because gravity causes sedimentation and the culture medium presses down on the cells. As a result, Ullrich says, scientists need a matrix or scaffold to support the growing tissue in three dimensions.
“In a weightless environment [like space], cells exhibit spatially unrestricted growth and assemble into complex 3-D [structures],” he says. This opens up the possibility of “macro-tissues” – organs – to be generated from these 3-D cell aggregates. Ullrich says.
The UZH test tubes of Ullrich’s experiment returned to Earth at Cape Canaveral, Fla., in April, but covid-19 restrictions on travel prevented the safe, temperature-controlled transport of the samples to Zurich for detailed analysis. Ullrich’s team, however, could confirm from remote, virtual observation that the samples had grown more bone, cartilage and other living tissue than would have been possible in the same amount of time on Earth. Ullrich is cautious with his analysis – “looking good,” is all he’s willing to say for now.
Another ongoing stem cell experiment in space comes from the lab of Alysson Muotri at UCSD. Muotri’s team works with stem cells that differentiate into brain tissue. “If we understand how microgravity can speed up [cell] maturation, we can understand [its] effect in the brain of the astronauts, but also . . . use that as a model to understand diseases that have long onset, such as Alzheimer’s or dementia,” he says. Apart from the NASA collaboration, Muotri has another stem cell experiment going on at the ISS. The first payload of that went up in late 2019, and he expects to send a follow-up by the end of 2020, before his NASA project early next year.
Room is limited on ISS, so one of the challenges in biomedical space research is keeping the experiments’ physical footprints as small as possible.
This happens using a specialized “research-in-a-box” module, called CubeLab, where the stem cell experiments are run while in orbit. The CubeLab is small enough “to fit in the trunk of my car,” Jamieson says. Within it, the physical parts of the experiment, as well as the automation and remote monitoring of the system, have to be precisely calibrated.
Observing and monitoring the experiments from afar is a major challenge, Jamieson adds, because, unlike in a lab on Earth, the scientists cannot pop in and out as needed, and limited adjustments can be done remotely.
“Sometimes microgravity can be a bummer,” Muotri says.
For instance, gravity on Earth plays a role in keeping electrodes, necessary to record electrical activity, in place in the tissues. “In space, they’re going to be floating,” Muotri says, which means, for accurate readings, scientists and engineers have to figure out ways to keep them attached to the tissues.
Looking ahead, could stem cells altered or grown in space be used in humans to cure ailments or for other reasons? It’s too early to say, but Ullrich believes it may happen one day.
Scientists hope that these experiments will help develop customized treatments, therapies and even medicines for patients with specific requirements, for whom generic medications and treatments are often not enough. “Transplantation . . . is of course the greatest possible goal,” Ullrich says, “but [these tissues] also serve testing in precision medicine or to replace animal experiments.”
Jamieson adds: “In this unique environment 250 miles above us, [we might be] able to discover truths about biology that we never understood before.” And that could lead to new drugs, new antibodies, new therapies. “I really do think that [space, and the ISSCOR lab in particular] is . . . a great place to do science.”