Stem Cell Treatment Study for Peripheral Artery Disease Underway

Indiana University, February 10, 2006

Peripheral artery disease affects tens of thousands of people. Also referred to as PAD, the disease affects blood circulation, generally in the legs resulting in sores, ulcers, and in some cases amputations. For those that are suffering, a unique clinical trial being conducted at the University of Indiana involving stem cell injections as a treatment may be the answer.

Half of the projected 10 million afflicted Americans who are diagnosed have no symptoms, but others report varying levels of pain as well as other symptoms which include numbness and sores on the legs and feet. The disease is caused by atherosclerosis which can lead to heart attack by clogging and hardening the arteries.

Dr. Michael, who is an assistant professor of surgery and a researcher at the Indiana Center for Vascular Biology and Medicine at the medical school, is leading the stem cell trial. Weight loss, eliminating smoking, and maintaining a proper diet are initial suggestions for management of the disease. Cholesterol-lowering drugs may be prescribed if appropriate. An angioplasty procedure that expands the blood vessels or an artery bypass graft may be treatment alternatives if the disease continues to progress.

However, Dr. Michael says that the surgical measures are not feasible for as many as 12 percent of those individuals afflicted, and that 30,000 to 50,000 people in the U.S. receive amputations due to PAD. The quality of life for a person fighting terminal cancer is comparable to that of someone who is severely affected by PAD.

With the potential to generate the cells that compose the lining of blood vessels, specialized descendants of stem cells called progenitor cells are being used in the IU trial. These "parent" cells can produce new specialized cells in the body when required and fall beneath the class of adult stem cells.

The patient is placed under general anesthesia and bone marrow is extracted from the patient’s hip, the progenitor cells and adult stem cells are separated from the bone marrow in a laboratory procedure while the patient re-awakens. Dr. Michael and his colleagues then administer one injection of the cells into the patient's leg. They are then evaluated on several occasions for a period of 12 weeks. Seven individuals have already undergone the procedure, and the doctors anticipate treating a total of 10 patients in the trial.

Initially, the tests will be considered a phase 1 trial, with the principal function being the validation of safety for the procedure. Wound healing and blood vessel development will be the indicators that the doctors will observe in this preliminary phase as well.

However, said Dr. Michael, "We think this is a very promising treatment that could help patients with severe peripheral artery disease for which there is now no effective therapy."

The new development of blood vessels was observed in other laboratory tests as well as earlier studies in animals when the subjects were given stem/progenitor cell injections into their tissue. Also, fewer progenitor cells and stem cells circulate in the blood of those individuals already diagnosed with heart disease as well as those with an increased risk of developing heart disease.

"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, M.D., Ph.D., director of the vascular biology and medicine center and professor of medicine and of cellular and integrative physiology.

By introducing the stem cells and progenitor cells, the scientists at IU hope to counter the deficiency of those critical cells. By stimulating the production of special protein growth factors, the hope is that they will initiate the repair and replacement processes that encourage blood vessel repair and the growth of new blood vessels.

A larger number of patients will be enrolled in the trial next year if all is shown to be safe in this initial phase. Intravenous delivery is the next method to test with the hope that the cells will have a greater impact on circulation than local injection. Plans to integrate cells derived from fat tissue as well as from the umbilical cord are also being drawn up, as this would eliminate the necessity of the surgery required to extract bone marrow. Dr. Michael also stated that they are conducting research to discover ways to persuade the cells to generate more growth enhancing proteins prior to injection.