Stem cell aging can contribute to precancer and cancer when inflammation and other forms of stress disrupt the controls that keep blood-forming stem cells stable. In this program, Catriona Jamieson, M.D., Ph.D., of UC San Diego explains how these changes can drive myeloproliferative neoplasms toward acute myeloid leukemia and why spaceflight helps researchers study the process more quickly.

Blood-forming stem cells normally spend much of their time resting, ready to regenerate the blood and immune systems when needed. But prolonged stress can alter their behavior. A damaged stem cell may reproduce itself, accumulate additional mutations and eventually generate cancer.

Stem cells are essential because they can rebuild tissue. That same regenerative power becomes dangerous when a stem cell loses its normal controls. Instead of repairing the body, it can begin regenerating disease.

How Does Stem Cell Stress Contribute to Cancer?

Chronic inflammation and other forms of stress can activate genetic processes that help stem cells respond to injury. These responses may be useful for a short time, but they can become harmful when they remain active.

One source of instability lies within repetitive sections of DNA sometimes called the dark genome. These regions include remnants of ancient viruses that became embedded in the human genome over thousands of years. They usually remain quiet, but inflammation, aging and environmental stress can awaken them.

Cells respond by activating editing enzymes that help control these repetitive elements. APOBEC enzymes edit DNA, while ADAR1 edits RNA. These systems can help stem cells mobilize and regenerate tissue during a temporary stress response.

When that response becomes prolonged, however, the enzymes can begin changing the cells they are meant to protect. Abnormal blood-forming stem cells may reproduce, evade normal controls and accumulate changes that lead to more advanced disease.

Jamieson examines this process in myeloproliferative neoplasms, disorders in which the bone marrow produces too many blood cells. Some of these conditions remain stable for years, while others progress to acute myeloid leukemia.

What Role Does ADAR1 Play in Cancer?

ADAR1 can help malignant stem cells survive by editing RNA, supporting their growth and reducing signals that would otherwise alert the immune system.

The enzyme normally helps cells manage stress and distinguish the body’s own RNA from viral material. Cancer cells can take advantage of this protective mechanism. When ADAR1 remains active, malignant stem cells may continue reproducing while becoming harder for the immune system to recognize and destroy.

This ability may help explain both how cancer develops and why it can return after treatment. Conventional therapies may reduce a tumor or eliminate many cancer cells, but malignant stem cells can survive, rebuild the disease and produce new cancer cells.

At the same time, healthy stem cells may become exhausted and less able to support a strong immune response. Effective treatment may therefore require both stopping malignant stem cells and protecting the healthy regenerative cells the body needs.

Why Do Researchers Study Stem Cells in Space?

Spaceflight accelerates some of the biological stresses associated with aging, allowing researchers to observe changes that may take years to develop on Earth.

Jamieson and her collaborators have completed multiple missions to the International Space Station, sending blood-forming stem cells and tumor organoids into orbit. Small nanobioreactors allow researchers to monitor when cells are resting, dividing or activating pathways associated with malignancy.

These systems act as early-warning tools. By observing how cells respond to microgravity, radiation and other stresses, researchers can identify molecular changes before they become more difficult to treat.

The experiments show that spaceflight can accelerate stem cell aging and activate repetitive elements in the genome. These changes provide a faster way to study how stressed cells move toward precancer and cancer.

Can Some Stem Cells Resist the Effects of Stress?

Some astronauts appear to mobilize a resilient population of regenerative stem cells before and during spaceflight.

These cells may be better able to rebuild bone marrow and compete with damaged or mutated stem cells. Researchers are studying how to identify this population and determine whether it can be safely expanded or activated.

The finding presents a more complex picture of stress. Stress can contribute to mutations and malignant behavior, but it may also awaken defenses that help the body repair itself.

The goal is to strengthen the beneficial regenerative response without allowing cancer cells to hijack the same pathways. Understanding why some people mobilize these resilient cells more effectively could help researchers develop ways to protect healthy stem cells during aging, illness or cancer treatment.

How Could Space Research Help Develop Cancer Treatments?

Tumor organoids grown in space can reveal how cancers respond to stress and potential treatments more quickly than similar experiments on Earth.

Organoids are miniature models created from cancer cells. In experiments described by Jamieson, organoids grew rapidly in space and activated ADAR1, making the enzyme a visible target for treatment.

Researchers tested an investigational compound called Rebecsinib, which blocks the cancer-associated form of ADAR1. The compound comes from a metabolite produced by bacteria found in soil in Japan, connecting research that began in the ground to experiments conducted in orbit.

In preclinical studies, Rebecsinib stopped the growth of organoids representing metastatic breast cancer, glioblastoma and acute myeloid leukemia that had developed from a myeloproliferative neoplasm.

These findings do not yet establish how the treatment will work in patients. They do show how space-based experiments can expose cancer vulnerabilities, clarify drug responses and help researchers evaluate potential therapies more quickly.

Can Cancer Be Stopped Before It Advances?

Preventing cancer progression may depend on identifying and targeting abnormal stem cells before they produce aggressive disease.

Jamieson’s research connects stem cell aging, chronic inflammation, RNA editing and space biology around a central question: Can researchers recognize malignant stem cell behavior early enough to stop precancer from becoming cancer?

The answer may require a combination of approaches. Researchers need to block pathways that allow malignant stem cells to reproduce and hide from the immune system. They also need to preserve the resilient healthy stem cells that regenerate blood, bone marrow and immune defenses.

By studying these processes on Earth and in orbit, scientists are working toward treatments designed not only to shrink existing cancers, but also to stop the cells capable of starting or rebuilding the disease.

Watch: Stem-Cell Aging and Pathways to Precancer Evolution

For more information on advances in stem cell research, visit UCTV’s Stem Cell Channel.