EndoMac Progenitor: The Newly Discovered Cell

A nine-year collaborative project involving teams from the South Australian Health and Medical Research Institute (SAHMRI), The University of Adelaide, Baker Heart and Diabetes Institute, and La Trobe University has recently culminated in a groundbreaking discovery. The team has identified a new type of progenitor cell, EndoMac progenitor, which holds great promise for advancing regenerative wound healing applications. 

Dr. Sanuri Liyanage from SAHMRI highlighted the remarkable potential of EndoMac progenitor cells, explaining that they can transform into two distinct cell types: endothelial cells, which create blood vessels, and macrophages, which are immune cells that play a crucial role in tissue repair and defense. “These cells are crucial for forming new blood vessels whenever the body requires them,” she stated. 

Macrophages are the first immune cells produced by an embryo, playing a crucial role in defending the body against pathogens. After birth, these cells renew themselves to fight pathogens. For over a century, scientists have speculated that circulating stem cells in the bloodstream might be responsible for generating new macrophages. Early studies in mice confirmed that bone-marrow-derived stem cells contributed to macrophage production, continuing into adulthood. However, recent breakthroughs have shown that these bone-marrow cells are restricted to specific tissues, such as the skin, gut, and heart. 

Proof of a Century-Old Hypothesis 

Researchers have long since hypothesized the existence of progenitor cells in the vascular system, capable of differentiating into endothelial and immune cells, but definitive evidence had remained elusive—until now. Their research is shedding light on a surprising source of new macrophages in adulthood—stem cells that were established in the body long before birth. 

A team led by Professor Peter Psaltis from SAHMRI has recently identified these cells, known as EndoMac progenitor cells, hidden in the outer layer of aortas in adult mice. These cells seem to originate in the aorta during early development. As mice age, these progenitor cells circulate throughout the body, replenishing tissues with fresh macrophages. Unlike stem cells, which can transform into any type of adult cell, progenitor cells are more specialized, with the ability to differentiate into a subset of specific cell types, like immune cells and endothelial cells. 

To evaluate their potential for chronic wound healing and tissue regeneration, Liyanage and her first co-author, SAHMRI biomedical scientist Anna Williamson, along with a team from multiple Australian institutions, cultured EndoMac progenitor cells in the lab and created a small colony. When this colony was injected into the bloodstream of mice with restricted blood flow in their hind legs—a model mimicking diabetic wounds—the injuries healed faster than in control groups. Within two weeks, the circulating progenitor cells transformed into macrophages and endothelial cells, essential for repairing and lining blood vessels, demonstrating their critical role in accelerating healing. 

Significance of the Findings 

At sites of injury and poor blood flow, EndoMac progenitor cells rapidly proliferate to aid in healing and blood vessel regeneration. The findings are particularly promising for conditions like diabetes, where the body’s natural healing abilities are often compromised, as well as for patients struggling with chronic wounds. "This represents a significant advancement in our understanding of blood vessel regeneration and holds promise for creating more effective treatments that support the body's capacity to heal and maintain function over time,” Dr. Liyanage said. 

Importantly, these cells also lack the typical markers that cells have for self-recognition, making them a promising candidate for transplantation. Without these 'self' markers, EndoMac progenitors are less likely to trigger an immune response in the recipient, reducing the risk of rejection. Researchers believe this unique characteristic makes them particularly well-suited for stem cell transplantation therapies, as they are much less likely to be attacked by the immune system. 

The research team is currently expanding their studies to explore similar progenitor cells in skin and muscle tissue, with results expected in the next 10 months. A crucial next step is the search for EndoMac-like cells in human tissue, which has already shown promising indications. If successful, this could lead to groundbreaking therapeutic applications, particularly for patients suffering from chronic wounds or diabetes-related complications. 

The discovery of EndoMac progenitors further enhances our understanding of blood vessel regeneration and could revolutionize tissue repair and regenerative medicine in mammals.  

The team's findings were published in Nature Communications. 

Michael Luke Jose | Writer, The STEM Review