Nicole Mlynaryk, UC San Diego
For stem cell research at UC San Diego, the sky’s no longer the limit.
Over the last five years, the university has become a pioneer in performing stem cell research in space. In a series of successful launches, researchers have sent blood, brain and liver stem cells onto NASA’s International Space Station (ISS), where the unique environment of low Earth orbit (LEO) offers an unparalleled view into the molecular mechanisms of cancer and aging.
These pioneering experiments have now paved the way for a new era in health science research. On February 27, 2023, leaders of the UC San Diego Sanford Stem Cell Institute announced the launch of a new Astrobiotechnology Hub, which brings together academic, industry and government partners to drive scientific and commercial innovation in stem cell research.
The announcement came a day before key members of the hub present their plans at the 2023 Biocom California Global Life Science Partnering & Investor Conference. The event marks the first public meeting of leaders in stem cell research, biotechnology, aerospace and in-space manufacturing, with all groups coming together to build consensus and break new ground.
“The future of stem cell science is in space, and UC San Diego is uniquely positioned to address challenges in human health and disease, and advance discovery of modern therapeutics that will benefit countless patients around the world,” said Chancellor Pradeep K. Khosla. “It is through collaborations such as these that we will be able to accelerate the timeline between discovery and real-world impact.”
While UC San Diego has existing partnerships with NASA and aerospace companies Space Tango, Axiom Space and Sierra Space, the new Astrobiotechnology Hub brings all these key players together and creates avenues for new strategic collaborations with regional biotechnology companies and global manufacturers.
“The collaborations between our Sanford Stem Cell Institute and its space and biotechnology partners exemplify what UC San Diego’s collaborative and groundbreaking community does best — working to address a variety of problems with novel, and in this case, literally out-of-this-world tactics,” said Corinne Peek-Asa, Ph.D., vice chancellor for Research at UC San Diego.
The Astrobiotechnology Hub will also focus on expanding basic research findings into clinical trials and commercial products. This includes manufacturing novel drugs, biofilms, and stem cell therapies in space, where the conditions make assembly faster and more cost-effective.
“It’s becoming evident that space is a great place to do science and to translate discoveries into tangible goods,” said Catriona Jamieson, M.D., Ph.D., director of the Sanford Stem Cell Institute. “The next thriving ecosystem of stem cell companies will be 250 miles overhead.”
Why study stem cells in space?
When astronaut Scott Kelly returned from a year-long trip aboard the ISS, his body had grown two inches taller, but his cells appeared decades older. Lab tests revealed numerous molecular changes to his blood cells, including damaged DNA, shortened telomeres, and inflammation — all signs of rapid aging and precursors to cancer.
Increasing evidence shows that the lack of gravity and exposure to the sun’s radiation in space can accelerate aging in human stem cells and promote their transformation into cancer cells. But understanding this process is not only helpful in keeping astronauts healthy — it could also teach us how to treat cancer and aging on Earth.
Researchers at the Sanford Stem Cell Institute are now using space as an ‘aging accelerator.’ Their experiments will first confirm that the microgravity environment accurately mimics human aging, and then use it to further dissect the aging process. The studies will help scientists and clinicians understand stem cell aging and cancer without having to rely on lengthy and expensive clinical trials monitoring Earthbound humans as they age or develop disease in real time.
While sending cells into space might seem strange to some, the researchers point out that terrestrial labs already rely on artificial experimental manipulations to try to simulate the effects of aging.
“Whether we’re looking at aging mice, putting cell cultures under oxidative stress, or manipulating genes associated with aging, we’re always seeking ways to model these processes at a more efficient scale,” said Alysson Muotri, Ph.D., professor at UC San Diego School of Medicine. “Now we’re taking a different approach to speed up the aging process, and studying how it plays a role in cancer, liver disease and neurodegeneration.”
Assembling the team
While the Astrobiotechnology Hub welcomes new partners, it is built on a foundation of existing relationships between UC San Diego and several titans of the aerospace industry.
In 2019 — the same year NASA published the results of Kelly’s space trip — the university led its first launch of stem cells into space. A batch of stem cell-derived human brain organoids, or “mini-brains,” were sent aboard a SpaceX Dragon Capsule and delivered to the ISS, where they were stored and monitored for the next four weeks.
In a lab on Earth, cell cultures like these require constant maintenance by research staff, who ensure the cells are taken care of and getting all the nutrients they need to stay alive. To do this in space, the researchers rely on the CubeLab, a device designed and built by engineering company Space Tango to automate cell maintenance and allow researchers to monitor data remotely from Earth.
The researchers also began partnerships with Axiom Space and Sierra Space, two companies leading the way in aerospace. Through these interactions, a pipeline was established to send new batches of stem cells onto orbiting space stations. This only became possible in recent years with the advent of companies like SpaceX sending commercial rockets to and from LEO. Scientists could now take advantage of these frequent trips to restock the space stations by adding a shipment of stem cells along with the other cargo.
In recognition of these early successes, NASA awarded UC San Diego and Space Tango $5 million in 2020 to establish the Integrated Space Stem Cell Orbital Research (ISSCOR) program. As the first dedicated stem cell research laboratory in space, ISSCOR spearheaded several new experiments in space, taking place over a series of space launches in the following years.
Inspired by this growing line of work and UC San Diego’s longstanding reputation in stem cell research, philanthropist T. Denny Sanford gifted the university $150 million to establish the Sanford Stem Cell Institute in 2022. The institute houses six transformational centers, including an expanded ISSCOR center and a Stem Cell Fitness and Space Medicine Center, each focused on different aspects of stem cell function.
“Denny is a passionate and visionary supporter of stem cell research, and his gift has been integral to our work in San Diego and in space,” said Jamieson.
Much like a new planet, whose growing gravitational force pulls more and more matter towards itself, UC San Diego is now building on these early successes and attracting new talent into its orbit. The growing team includes global space leaders, academic researchers at other universities, and industry partners from the rich biotechnology community in San Diego.
“The progress isn’t incremental, it’s explosive,” said Jamieson. “I’ve never seen this level of scientific might coming together to support a new line of work.”
One key aim of the Astrobiotechnology Hub is to bolster in-space manufacturing, taking advantage of the unique properties of stem cells in space. Stem cell-based therapies have shown early promise in treating many conditions, but their success depends on having a large volume of high-quality stem cells to transplant into patients. As it turns out, stem cells seem to grow and proliferate more robustly in LEO, and the microgravity environment makes it easier to assemble three-dimensional tissue layers. These findings position space labs as a promising production site for stem cell therapies.
“We are now building an industrial engine to assess what aspects of scientific manufacturing can be done bigger, better and faster in space,” said Jamieson.
As new data pours in from the cosmos, the hub continues to expand its studies of immune dysfunction, cancer and aging across different cell and tissue types. The goal is that these insights will soon inspire new clinical interventions in the form of novel drugs and stem cell therapies.
One branch of research, led by Muotri, focuses on the effects of the LEO environment on neural stem cells and brain organoids.
“Our data shows that microgravity can accelerate the aging of brain cells,” said Muotri. “We can now use this to simulate neurological aging and create novel laboratory models for late-onset diseases such as Alzheimer’s and dementia.”
Muotri’s group already has four more space launches planned, with the next one scheduled for June. Future missions will explore the molecular and cellular mechanisms of neurodegeneration on Earth and in space.
Another line of research will investigate the effects of stress and aging on liver progenitor cells. This work is led by Tatiana Kisseleva, MD, PhD, professor of surgery at UC San Diego School of Medicine, and David A. Brenner, MD, president and chief executive officer of Sanford Burnham Prebys and former vice chancellor for Health Sciences at UC San Diego.
Kisseleva and Brenner study ailments of the liver, such as fibrosis and steatohepatitis, a type of fatty liver disease. They are interested in determining the impact of microgravity on liver function, which could provide insights into diseases on Earth, and the potential effects of space travel.
A final major research focus uses blood stem cells to study the molecular mechanisms of cancer. When stem cells in our bone marrow become mutated, they give rise to precancerous cells that can lead to leukemia. This process typically occurs over several decades on Earth, but happens much faster in space where cells are more exposed to the sun’s ionizing radiation. This offers Jamieson and colleagues the opportunity to look for biomarkers of cancer and immune cell malfunction in a compressed time frame.
“If we can find early predictors of cancer progression on the ISS, we are ideally positioned to rapidly translate them into clinical trials back on Earth at the Sanford Stem Cell Institute,” said Jamieson.
And they’re well on their way there. Jamieson’s team, in partnership with Space Tango, has now completed three NASA-funded launches of blood stem cells into space, with a fourth scheduled in March. The data they’ve collected, in conjunction with experiments done on Earth, has already revealed a particular protein, ADAR1, as a main driver of cancer proliferation in space.
ADAR1 helps control the body’s innate immune response, editing RNA molecules so they won’t be attacked by the immune system. This is useful in some contexts, but in disease states and the space environment, ADAR1 becomes overexpressed. This overactivity can then drive cancer cells to proliferate and develop a resistance to chemotherapeutic drugs. Once the researchers discovered this, they accelerated the development of a small molecule inhibitor of ADAR1, called Rebecsinib, which they recently showed can reverse the effects of the overactive protein.
“Space research was critical in helping us scale and refine this novel drug target,” said Jamieson. As part of Axiom Space’s AX-2 launch in May, Jamieson’s team will start collecting blood samples from astronauts to see if there are any changes in the immune regulation of their stem cells, particularly in the activity of ADAR1. The samples will be collected longitudinally to study the short and long-term dynamics of immune dysregulation in spaceflight.
These types of experiments are just the start of a new push toward drug discovery and manufacturing in space. The burgeoning field, fueled by cross-sector collaborations, seems fit to transform the medical and biotech industries.
“Together, we are creating something that not only provides an engine for economic growth but drives innovation to achieve the most important goal of all: benefiting patients,” said Jamieson. “The time to invest in space science is now.”