EndoMac Progenitors Found in Adult Mouse Aortas

Australian researchers have identified an entirely new cell type that addresses a significant gap in knowledge about how mammalian bodies repair themselves.

For more than 100 years, scientists had proposed that a cell of this kind might exist. An adult form has finally been discovered, concealed within the aortas of mature mice.

EndoMac progenitors and blood-vessel repair

The finding comes after nine years of research. The scientists have called the cells ‘EndoMac progenitors’ and are now looking for comparable cells in the human body.

“These cells have an important job, to help grow blood vessels when the body calls for it,” explains medical scientist Sanuri Liyanage from the South Australian Health and Medical Research Institute (SAHMRI).

“They are activated by injury or poor blood flow, at which point they rapidly expand to aid in healing.”

Liyanage and her colleagues extracted EndoMac progenitor cells from mice and grew them in the laboratory, where they developed into colonies. When the colonies were injected into diabetic mouse models, they substantially enhanced wound repair.

The role of macrophages in mammalian tissues

To see how an EndoMac progenitor cell functions, it is first necessary to look at macrophages.

Macrophages are the earliest immune cells created in an embryo and are vital to development. In adult mammals, most tissues contain macrophages formed at this very early developmental stage. Following birth, these resident groups sometimes replenish themselves, remaining prepared to consume pathogens.

Around a century ago, however, researchers proposed that stem cells travelling through mammalian blood might generate fresh macrophages, renewing the cells already residing in the body’s different tissues.

For years, scientists thought these circulating macrophage-producing cells - previously identified in mouse embryos - remained present during adulthood because they had been established in the bone marrow. More recent evidence, however, indicates that bone marrow-derived stem cells are limited to only a small number of tissues, among them the gut, skin and heart.

Evidence from the mouse aorta

Some scientists now believe that adult macrophages may arise from as-yet undiscovered stem cells that became established in the body well before birth. Although the idea remains strongly debated, the Australian mouse study lends support to a shift in the prevailing view.

The results indicate that embryonic macrophage progenitor cells become established in the heart’s aorta during early development. As mice grow older, these circulating stem cells then supply tissues with new macrophages.

The researchers say EndoMac progenitors lack ‘name tags’, meaning they could be transplanted without concerns that the immune system would attack the foreign material.

Liyanage, her co-first author and SAHMRI biomedical scientist Anna Williamson, and collaborators from several Australian institutions cultivated EndoMac progenitor cells in the laboratory, producing a small colony.

They injected this colony into the bloodstream of a mouse whose hind-leg circulation had been restricted to imitate a ‘diabetic wound’. The injury in its leg healed more quickly. Within two weeks, the circulating stem cells had become macrophages and endothelial cells, which form the lining of blood vessels.

The team is now examining whether an equivalent cell occurs in the human aorta. Those results have not yet been published, although the researchers have suggested that early findings are encouraging.

“In theory, this could become a game-changer for patients suffering from chronic wounds,” says Liyanage.

“We're excited to continue exploring the potential of these cells. It's early days, but the implications could be massive.”

The study was published in Nature Communications.