An estimated 10 million Americans are affected by the poor blood circulation -- generally in the legs -- of peripheral artery disease (PAD). It is caused by atherosclerosis, the clogging and hardening of arteries that can lead to heart attacks. Although about half of those with PAD have no symptoms, others report varying levels of pain and other symptoms including numbness and sores on the legs and feet.
Early treatment is similar to actions to prevent heart disease, such as a better diet, stopping smoking cessation, weight loss and if appropriate, cholesterol-lowering drugs. If the disease progresses, patients may receive an artery bypass graft or an angioplasty procedure that widens the blood vessel.
But as many as 12 percent of PAD patients cannot undergo such surgical procedures, and 30,000 to 50,000 people in the United States receive amputations annually due to PAD, said Michael Murphy, M.D. assistant professor of surgery and an investigator at the Indiana Center for Vascular Biology and Medicine at the medical school, who is leading the stem cell trial. For many of these severely affected patients, their quality of life is similar to patients battling terminal cancer, he said.
The cells used in the IU trial include adult stem cells, which are "parent" cells that can create new specialized cells when needed by the body. In the IU trial, researchers are using stem cells -- and slightly more specialized descendants called progenitor cells -- that can create the cells that make up the lining of blood vessels.
In the clinical trial at IU School of Medicine, Dr. Murphy and his colleagues extract bone marrow from the patient's hip while the patient is under a general anesthetic. The adult stem cells and progenitor cells are separated from the bone marrow in a laboratory procedure while the patient recovers from the anesthesia. The cells then are injected into the patient's leg.
Patients will receive one injection and then will be evaluated on several occasions for 12 weeks. IU doctors expect to treat 10 patients in the trial, and seven have already undergone the procedure. (Two of the patients were treated at Duke University where Dr. Murphy was previously on faculty.) Although the researchers will be looking at such indicators as blood vessel growth and wound healing, the current trial is a initial, or phase 1, test meant primarily to demonstrate that the procedure is safe.
However, said Dr. Murphy, "We think this is a very promising treatment that could help patients with severe peripheral artery disease for whom there is now no effective therapy."
Previous studies in animals and other laboratory tests have indicated that injections of the stem and progenitor cells into tissues resulted in development of new blood vessels.
In addition, research has shown that people with heart disease, or who are at increased risk of heart disease, tended to have fewer of the blood vessel stem and progenitor cells circulating in their blood.
"Our hypothesis is that people run out of these cells, or they have inadequate supplies -- perhaps because of genetic factors. As a result, they can't repair or replace damaged blood vessel cells, and heart disease ensues," said Keith March, M.D., Ph.D., director of the vascular biology and medicine center and professor of medicine and of cellular and integrative physiology.
The IU scientists hope to counteract the shortage of those critical cells by introducing the stem cells and progenitor cells taken from the patients' bone marrow. In turn, it's hoped, they will promote blood vessel repair and the growth of new blood vessels by stimulating the production of special protein growth factors.
By introducing the stem and progenitor cells taken from the patient's bone marrow, the IU scientists hope that they will be able to jump-start those repair and replacement processes. They expect that would occur when the bone-marrow derived cells stimulate the production of special protein growth factors that would stimulate the development of new blood vessels.
If the current trial shows that the procedure is safe, the next step would be to test the procedure in a larger number of patients next year, Dr. Murphy said. In that test, the cells would be delivered intravenously in hopes that it would have a broader impact on circulation than a local injection. In addition, he and his colleagues hope to conduct trials using cells taken from fat tissue and from umbilical cord blood to avoid the surgery necessary for bone marrow extraction. Research also is underway to determine whether the cells could be modified in ways to encourage them to produce more growth enhancing proteins before they are given to the patients, Dr. Murphy said.