Tapping The Potential Of Adult Stem Cells
Can adult stem cells help regenerate the damaged blood vessels in patients with peripheral vascular disease?
A multidisciplinary team of researchers at the Indiana Center for Vascular Biology and Medicine is experimenting with a novel adult stem cell therapy, using patients' bone marrow cells that are involved in arterial formation and repair. The Stem Cell Mediated Angiogenesis Study is an FDA-approved Phase I clinical trial to examine how safe and effective adult stem cells are for stimulating the development of new blood vessels in the legs of patients with severe peripheral vascular disease--a painful condition that, according to the American Heart Association, affects approximately 12 million people. When blocked or destroyed, arteries in the leg are unable to transport essential nutrients and oxygen, resulting in tissue death and gangrene. Many patients suffering from advanced peripheral vascular disease often exhaust all conventional means of therapy and face amputation.
Researchers hope that the specialized adult stem cells--known as endothelial progenitor cells (EPCs), involved in the repair of the inner lining of blood vessels--will help restore enough blood flow to lower limbs to help regenerate blood vessels and avoid amputation.
One day, the innovative therapy might benefit other areas of the body, such as the heart muscle.
To learn more about the trial, the Post spoke with Michael Murphy, M.D., at the Indiana Center for Vascular Biology and Medicine at Indiana University School of Medicine.
Post: Could you outline your research utilizing adult stem cell-based therapy to treat cardiovascular disease?
Murphy: Basically in the last five years, researchers have isolated a cell in the bloodstream of humans called an endothelial progenitor cell--a special type of stem cell. Subsequent studies have demonstrated that the endothelial progenitor cell, or EPC, comes from the bone marrow. Clinical evidence from an NIH study showed that patients who have a greater number of cardiovascular risk factors--high blood pressure, diabetes or cigarette smoking--have fewer endothelial progenitor cells. The conclusion was that these cells are involved with arterial repair and may help prevent the development of atherosclerosis. The cells also participate in the development of new blood vessels. Animal studies have demonstrated that when EPCs from bone marrow are injected into lab animals, they develop new blood vessels in response.
Post: How do you retrieve and administer the adult stem cells in your study?
Murphy: Under anesthesia, we remove about 500 cc, or one-half a liter, of bone marrow from the patient--about 2 to 2 1/2 cups of bone marrow. We process the bone marrow in our stem cell laboratory at University Hospital. We separate out what we call the buffy coat--the mononuclear cell layer--by spinning the cell preparation at very high speeds.
To administer, we basically inject the cells, or the mononuclear cell fraction containing a subpopulation of progenitor stem cells, right into the calf muscle of the affected leg that has insufficient blood flow. In the future, we plan to grow the cells in culture and increase the number of endothelial progenitor cells before injecting. Right now, we have strict limitations on what we can do from the FDA, because this is the first such study in the United States.
There is evidence the injected progenitor ceils directly incorporate into new capillary beds and produce the necessary protein messengers--so-called cytokines--that induce existing blood vessels to grow.
By using the cells from the patient's own bone marrow, we avoid the problem of rejection and so avoid the ethical issue of using embryological cells.
Post: Is this one of the first U.S. stem cell therapy-based trials?
Murphy: Yes. It is what we call translational medicine and modeled after a Japanese study published in 2002. Unfortunately, the U.S. is several years behind our colleagues in Japan and Germany, especially in adult and embryological stem cell research. |
