EndoMac Progenitors Found in the Aorta of Adult Mice

Researchers in Australia have identified an entirely new cell type, addressing a significant gap in knowledge about how mammalian bodies repair themselves.

For more than a century, scientists had proposed that such a cell existed. An adult form has now finally been discovered, concealed within the aorta of adult mice.

The finding took nine years to achieve. The researchers have called the cells ‘EndoMac progenitors’, and are now looking for comparable cells in the human body.

EndoMac progenitors and blood-vessel repair

“These cells have an important job, to help grow blood vessels when the body calls for it,” explains medical scientist Sanuri Liyanage of 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’s team extracted EndoMac progenitor cells from mice and grew them in laboratory culture, where they developed into colonies. Injecting these cell colonies into diabetic mouse models led to a dramatic improvement in wound healing.

How macrophages develop in mammals

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

Macrophages are the earliest immune cells made by an embryo, and they play a vital role in development.

Most mammalian tissues retain macrophages created at this very early point throughout adult life. Following birth, these resident groups can renew themselves from time to time, remaining prepared to consume pathogens.

Roughly a century ago, scientists suggested that stem cells circulating in mammalian blood might generate new macrophages, replenishing populations already present across the body’s tissues.

For years, researchers thought these circulating macrophage-producing cells - previously identified in mouse embryos - continued into adulthood because they were established in bone marrow.

However, newer evidence indicates that stem cells derived from bone marrow may be limited to only a small number of tissues, including the gut, skin and heart.

Some scientists now believe adult macrophages may instead arise from as-yet-unidentified stem cells established in the body well before birth.

Evidence from the mouse aorta

Although this theory remains fiercely contested, the Australian mouse study lends weight to a potential shift in understanding.

The results indicate that embryonic macrophage progenitor cells are planted in the heart’s aorta during early development. As mice grow older, these circulating stem cells then deliver fresh macrophages into tissues.

Researchers say EndoMac progenitors lack ‘name tags’, meaning they could be transplanted without the immune system attacking the foreign material.

Liyanage, co-first author and SAHMRI biomedical scientist Anna Williamson, and colleagues from several Australian institutions grew EndoMac progenitor cells in the laboratory to form a small colony.

They then injected that colony into the bloodstream of a mouse with restricted circulation in a hind leg, designed to mimic a ‘diabetic wound’. The injury in its leg recovered more quickly. Within two weeks, the circulating stem cells had become macrophages and endothelial cells, which form the lining of blood vessels.

The researchers are now examining whether an equivalent cell is present in the human aorta. Their results have not yet been published, although the team has indicated 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.