Growth-factor therapy improves endothelial cell production and mobility in arterial disease

March 12, 2006

ATLANTA-sing a growth factor to stimulate production of circulating endothelial progenitor cells increases the numbers of these vascular regenerative cells, improves mobility, and potentially could improve blood vessel function in patients with peripheral arterial disease (PAD). Scientists at Emory University will present results of a recent clinical trial with endothelial progenitor cells and PAD at the American College of Cardiology Meeting in Atlanta.

Scientists have discovered recently that a healthy crop of circulating endothelial progenitor cells ÐÐ the stem, or precursor cells to those that line the insides of blood vessels ÐÐ is essential to a person's overall cardiovascular health and unimpeded blood circulation. Endothelial cells enable communication between the vessels themselves and circulating blood cells, allowing the blood to flow smoothly.

Individuals with PAD have decreased blood flow to the muscles of the legs, caused by the blockage or narrowing of the arteries, often leading to intermittent pain during walking. Recent studies show that when muscles do not receive enough blood, the body makes its own growth factors that stimulate the bone marrow to release endothelial progenitor cells that home to the damaged vessels and either make new blood vessels or repair the damaged ones.

The Emory scientists hypothesized that if the body uses its own growth factors to stimulate production of endothelial progenitor cells, then endothelial dysfunction in PAD would improve if additional progenitor cells were mobilized through a boost from growth factor therapy.

In a double-blind, placebo-controlled study, the researchers randomized 45 PAD patients to receive either the growth factor GM-CSF (granulocyte macrophage colony stimulating factor) or placebo. Each group of 15 patients received a different dose of GM-CSF or placebo three times a week for three weeks. Before therapy, the PAD patients had severely depressed levels of circulating endothelial progenitor cells.

The researchers found that the GM-CSF treatment increased total leucocyte (white-blood cell) count and the total number of circulating endothelial progenitor cells. Patients who received the growth factor therapy also experienced an improvement in the ability to walk without pain. They found no significant difference in results between the three dosage groups. The placebo group experienced no improvement after therapy.

The Emory team was led by principal investigator Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine, and cardiology fellow Veerappan Suramaniyam, MD.

"This research demonstrates that growth factor therapy can improve endothelial dysfunction and suggests that endothelial progenitor cells, by enhancing repair, may contribute to endothelial healing," said Dr. Quyyumi. "Our next step will be to continue studying whether stem cell mobilization can be used to improve vascular function and reduce the risk of atherosclerosis.

Emory University Health Sciences Center

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