Is space the place for stem cell manufacturing? Scientists will soon test that on the ISS

The world’s second-ever private astronaut mission to the International Space Station will not only ferry up the first Saudi Arabian woman to go to space but also a first-of-its-kind experiment that will test whether scientists can create induced pluripotent stem cells, or iPSCs, in microgravity. The experiment is part of a series that could eventually lead to new ways to manufacture stem cells en masse.

The experiment is set to take flight May 21 aboard a SpaceX Dragon spacecraft with Axiom Space’s Axiom Mission 2, or Ax-2. It will remain there for five days before being brought back down to Earth, where researchers from Cedars-Sinai Medical Center in Los Angeles will analyze how the cells were affected by microgravity.

IPSCs are a type of stem cell that’s developed from reverting body cells—typically skin cells, or fibroblasts—back to their pre-differentiated state. From there, they can be reprogrammed into any type of cell, making them a potential replacement for ethically divisive embryonic stem cells in drug research and regenerative medicine.

Why study iPSCs in microgravity? One of the reasons the cells haven’t yet become commonplace in medical and research applications is they’re notoriously difficult to produce in large quantities on Earth, as it’s hard to recapitulate the human body’s unique environment in a 2D cell culture. That’s less of a problem in microgravity, where the cells can proliferate in a 3D space that’s more similar to their natural growth conditions.

The experiment aboard Ax-2 will include a set of skin cells—or fibroblasts—and a set of stem cells. The scientists will study the fibroblasts to understand how microgravity impacts transfection, a process where DNA is added to differentiated cells to reprogram them back into stem cells. They’ll analyze the stem cells to see how microgravity affects their ability to grow and proliferate.

Five days doesn’t seem like long, but, according to the Cedars-Sinai team behind the study, it’s likely enough time to see how the cells are affected.

“We know that stem cells are very adaptable to whatever environment they’re put into,” Arun Sharma, Ph.D., one of the researchers involved in the project, said in a May 11 press release from the ISS. “Their genes change very quickly, within hours. So, the changes we see in those five days may be enough for us to get really good scientific data.” 

There’s evidence already that microgravity might be an ideal growing ground for stem cells. Previous studies by the Mayo Clinic looking at a different type of stem cell called mesenchymal stem cells, or MSCs—cells in the bone marrow that eventually differentiate into the various types of blood cells—found that MSCs grown on the ISS survived better and were more readily differentiated than those on the ground.

While the idea of using microgravity to manufacture iPSCs and MSCs is exciting, there have been concerns that the environment can cause carcinogenic changes to other types of stem cells in vivo. Another team of researchers, this time from the Sanford Stem Cell Institute at the University of California, San Diego (UCSD), plans to use the forthcoming mission as an opportunity to investigate this. They’ll take blood samples from the Ax-2 crew before, during and after their spaceflight to measure changes in enzymes that edit RNA and DNA to see whether they trigger cancer-causing mutations or speed up the aging process in blood stem cells.

The UCSD team will compare those results to another experiment they’re conducting on the mission, this one involving 3D tumor organoids of intestinal cancer, leukemia and breast cancer. They’ll measure the activation levels of RNA- and DNA-editing enzymes along with cell cycle changes, which in the future could be used as biomarkers for early detection. They’ll also study whether drugs like Bristol Myers Squibb’s JAK inhibitor Inrebic or Aspera Biomedicines' small-molecule ADAR1 inhibitor rebecsinib can halt the formation of cancerous cells.

“Space is an accelerating environment where we’ll be able to identify new therapies and new ways to target cancer faster, maybe even at the pre-cancer stage,” Catriona Jamieson, M.D., Ph.D., Sanford Stem Cell Institute director and lead researcher on the project, said in a press release. “We saw that cancer spreads faster in space; now we want to know how we block it.”