Stem cells have high hopes riding on them as a possible treatment for ailments such as cardiovascular disease. But recent findings suggested that stem cells might be what are to blame for the onset of vascular disease in the first place.

The authors reported that, contrary to accepted wisdom, scar tissue on atherosclerotic plaques, which decreases the levels of blood flow through the arteries, does not result from smooth muscle cells de-differentiating, or putting their developmental program into reverse gear and becoming more progenitor-like.

Instead, the team identified a new type of stem cell in the vasculature, which they named multipotent vascular stem cells. Their research indicated that it is those stem cells that go bad in the environment created by arterial plaques.

Most of the work was done in animals, but senior author Song Li and his team confirmed that the multipotent vascular stem cells can be found in human tissue.

Because they are located in the arterial wall, those stem cells "are in contact with blood" and consequently are very exposed to inflammatory signals, Li told BioWorld Today. He contended that is how a cell type that is generally thought of as a major contributor to health can go so very wrong in that instance.

Li is a professor of bioengineering at the University of California at Berkeley and the senior author of a paper describing his team's work, which appeared in Nature Communications on June 6, 2012.

The current theory is that vascular disease such as atherosclerosis starts as an immune response to LDL cholesterol. Macrophages respond to LDL cholesterol accumulation in the walls of arteries, leading to the buildup of foamy plaques.

Logically enough, most therapies to treat or prevent vascular disease focus on reducing the levels of LDL cholesterol – statins, anyone? – or otherwise treating the plaques. (See BioWorld Today, Jan. 13, 2012.)

But Li argued that his work suggests a wholesale rethinking of that approach. "It is plain that these stem cells should be the main target" for therapeutic approaches to vascular disease, he said.

Scientists have known for quite a while now the phenomenon of vascular remodeling plays a role in vascular disease. Such remodeling consists of proliferating cells, which divide and form scar tissue within plaque-ridden blood vessels.

The ultimate consequence of such remodeling is that less blood can flow through the vessels, which leads to hypertension and, in some cases, more serious consequences such as stroke.

The main cell types behind such remodeling were long thought to be smooth muscle cells that have de-differentiated, or moved toward a more stem cell-like state, prompted by the inflammatory signals in plaques.

But the direct evidence of smooth muscle cells in reverse gear was scant. And so, Li and his team approached the question of the origin of such cells in two complementary ways.

They looked at proliferating cells from the vessels of transgenic mice with a fluorescent marker in their smooth muscle cell. When cells were cultured under conditions that encouraged them to keep dividing, some did. But none of them had the marker that identified them as former smooth muscle cells, meaning that they must be descended from some other cell type.

Searching for cells with molecular markers of that cell type, Li and his colleagues identified a stem cell that was able to develop into smooth muscle, nerve, cartilage, bone and fat cells in culture. Li and his team demonstrated that the cells they identified could turn into cartilage cells in animals – which may explain the reason why arteries harden in vascular disease.

Li theorized that, like adipose stem cells, the multipotent vascular stem cells can turn into bone cells as well, and that may be the reason why arteries in late-stage vascular disease can turn brittle. His team, in work that is "ongoing" in his laboratory, is testing that notion.