With the hope of growing small blood vessels and restoring circulation in the legs, two patients were the first to be treated by transplanting a purified form of the subjects’ own adult stem cells into the leg muscles. Both patients suffered from severely blocked arteries and faced possible leg amputations. This first U.S. trial of the technique that has worked on laboratory animals was conducted by Northwestern University Feinberg School of Medicine.
“They’re at the end of the therapeutic road and they’re ultimately facing potential amputation,” said Douglas Losordo, M.D., the Eileen M. Foell Professor of Heart Research and principal national investigator for the study. “This is hopefully a way to help them avoid that.”
Losordo is director of the university’s Feinberg Cardiovascular Research Institute and director of cardiovascular regenerative medicine at Northwestern Memorial Hospital.
“The stem cells themselves can assemble into blood vessels,” Losordo said. “They can also secrete growth factors that stimulate and recruit other stem cells to come into the tissue and help with the repair. It’s an amazing biology we’re trying to leverage in these folks.”
The approach has proven to be effective in mice and rats during pre-clinical studies where stem cells were transplanted into the limbs of the animals.
“Based on that, we think it has a good chance of helping humans,” Losordo noted.
“This is a dreadful disease in which the profession has failed to offer much in the way of relief for these patients,” Losordo said. “We’re hoping this will have some impact.”
The trial is being conducted at 20 different sites nationally. The first two patients received their transplants at Northwestern Memorial Hospital.
Wounds that don’t heal, the breakdown of tissue, and gangrene can be the result of severely blocked arteries in the leg and sharply diminished blood flow. More than 100,000 limbs are amputated in the United States due to the painful condition call critical limb ischemia (CLI).
Affecting 1.4 million people, the emerging health problem is serious. By the time they reach the age of 70, and estimated 15 percent of the population will suffer from this disease.
Patients who have exhausted all other medical options including angioplasty, stents and bypass surgery to repair blocked circulation in their legs were the target of the Northwestern-led phase I/IIa study, which will include 75 people with CLI around the country.
Affecting about 10 million people in the United States, critical limb ischemia is the result of advanced peripheral artery disease. In peripheral artery disease, people develop blockages in their arteries and vessels that slow or stop the blood flow to their legs.
The condition is called CLI when they have wounds on their legs or feet that will not heal and pain at rest in their lower legs. If left untreated, CLI can result in a patient having toes, a foot or even a leg amputated.
People begin to experience pain when they walk, then when just sitting, as CLI progresses. Since blood flow decreases when people lie down, the pain is the worst at night. In order to lessen the pain and aid in blood flow, some even sleep in chairs.
“Peripheral artery disease is a big health problem,” Losordo said. “There is an emerging awareness of this disease on public health.”
The risk of developing the condition is elevated by high blood pressure, diabetes, high cholesterol and smoking.
However, Losordo points out that, “some people don’t smoke, have diabetes or high blood pressure and can still have blocked arteries in their legs.”
Losordo uses the subject’s own purified stem cells for the randomized, double blind, placebo-controlled trial. CD34+ stem cell from bone marrow are first released into the blood stream by a stem cell stimulating drug. The patient takes this drug for five days prior to the stem cell extraction. Then, the CD34+ enriched blood is obtained by way of an intravenous line that is inserted into a subject’s vein to collect blood through a machine that removes a population of blood cells. Losordo further selects and enriches the cells to select only CD34+ cells.