Patients with chronic myocardial ischemia (CMI) suffer the most severe form of coronary disease. In this condition, the blockages of coronary vessels feeding the heart are so severe, or the patients are so sick, that they have few or no options for treatment or improvement. Therapeutic angiogenesis is a new approach aimed at stimulating the growth of new blood vessels (angiogenesis) into the sickest areas of the heart, thus replenishing the vital blood supply. In laboratory studies, this approach has been shown to successfully treat heart disease, stroke, and impaired blood flow to the legs, or peripheral arterial disease.

Now, the largest national stem cell study in patients with CMI has shown the first evidence that transplanting a potent form of angiogenesis-stimulating adult stem cells into the heart muscle of subjects with severe angina — chest pain due to blocked coronary arteries — results in less pain and an improved ability to walk. The group of patients who received these cells also experienced fewer deaths than those who didn’t receive stem cells. Findings were presented on November 17 at the American Heart Association Scientific Sessions 2009 in Chicago. The study was supported by Baxter Healthcare Corporation.

“This is the first study to show significant benefit in pain reduction and improved exercise capacity in this population with very advanced heart disease,” said principal investigator Douglas Losordo, M.D., the Eileen M. Foell Professor of Heart Research at the Northwestern University Feinberg School of Medicine and a cardiologist and director of the program in cardiovascular regenerative medicine at Northwestern Memorial Hospital, the lead site of the study.

Preclinical studies have indicated that human stem cells, called CD34+ cells, can stimulate the growth of small blood vessels in damaged areas in the heart, improving blood flow and function. In the 12-month, phase 2, double-blind trial, 167 patients at 25 study sites across the United States received either their own purified CD34+ cells or placebo. The CD34+ cells were injected into 10 locations in the heart muscle. A sophisticated electromechanical mapping technology called NOGA identified where the heart muscle is alive but not functioning due to insufficient blood supply. The patients, whose average age was 61 years, had exhausted their options for revascularization and had lifestyle-limiting angina despite optimal medical therapy.

Twelve months after the procedure, the treated subjects were able to double their exercise time on a treadmill compared to the placebo group. It also took twice as long until they experienced angina on a treadmill compared to the placebo group, and, when they felt pain, it went away faster with rest. In addition, they had fewer overall episodes of chest pain in their daily lives.

Out of the estimated 1 million people in the U.S. who suffer from chronic, severe angina, about 300,000 cannot be helped by any traditional medical treatment such as angioplasty, coronary artery bypass surgery, or stents. The subjects in this phase 2 study were considered Class 3 or 4 patients, meaning they experienced chest pain while performing normal activities, such as while brushing their teeth, or even while resting.

Dr. Losordo, who is also director of the Feinberg Cardiovascular Research Institute, said this study provides the first evidence that a person’s own stem cells can be used as a treatment for angina in patients with no other medical options. He cautioned, however, that the findings require verification in a larger phase 3 study.

“With this well-designed, placebo-controlled study, the field of regenerative medicine and therapeutic angiogenesis have converged,” said Dr. William W. Li, President and Medical Director of the Angiogenesis Foundation. “We see the evidence that adult stem cells play a new role in the field of angiogenesis.”