Scientists Investigate Adult Stem Cells Potential to Heal Diseased Heart

PharmaLive, January 15, 2007

In order to determine if a subject’s own stem cells can treat a form of severe coronary artery disease, Rush University Medical Center is becoming one of the first medical centers in the country to participate in The Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia (ACT34-CMI) Trial.

In an effort to improve symptoms and clinical outcomes in subjects with chronic myocardial ischemia (CMI), a severe form of coronary artery disease, the trial is designed to investigate the safety, tolerability, and efficacy, of blood-derived selected CD34+ stem cells in treatment. It is the first human, Phase II adult stem cells therapy study of its kind in the U.S.

"What we’re hoping is that these stem cells will be able to stimulate the growth of new blood vessels to bring more blood and oxygen to the heart muscle, so that these patients will have a better quality of life and less chest pain," said Dr. Gary, director of the Rush Cardiac Catheterization Lab and study investigator.

Resulting in limited blood flow to the heart due to the narrowing of the coronary arteries, myocardial ischemia is a serious heart condition. Hundreds of thousands of new people are affected each year. Despite optimum medical intervention, insufficient flow of oxygen-rich blood to the heart still persists in a person who suffers from chronic myocardial ischemia.

Involving adult subjects with severe coronary artery disease, the experiment is a randomized, double-blind, placebo-controlled study. Subjects are those who are not suitable candidates for conventional procedures to improve blood flow to the heart such as angioplasty, stents, or coronary artery bypass surgery. The subjects are also currently on the maximum medical therapy allowable for the condition with respect to their current conventional treatment parameters.

The first step for all study subjects is to determine the severity and baseline frequency of the aginal episodes. A commercially produced protein (granulocyte colony stimulating factor) is then administered in a series of subcutaneous injections. The protein helps to release CD34+ stem cells (also known as endothelial progenitor cells) from a subject’s bone marrow into the bloodstream.

Next, the scientists collect and enriched preparation of cells that contain CD34+ stem cells from the patient’s blood stream by using a cell separation system not unlike the automated systems that are used when people donate red blood cells or platelets. The collection process is called apheresis. Once collected, the stem cells are further processed to select the CD34+ stem cells that will be used for the investigational therapy.

Once the cells are ready, Gary uses a three-dimensional non-surgical system map that is catheter-based to identify the damaged areas of the subjects heart. The cells are then injected into the respective location as determined by the mapping technology. The areas of the heart that have been identified as having poor blood flow are then injected using a special investigational catheter that delivers a placebo, or the actual CD34+ cells.

"This targeted approach increases the treatment's effectiveness by delivering the stem cells exactly where they are needed," says Gary. It works like a human GPS system.

Receiving either a placebo or one of two dosing levels of CD34+ stem cells, the subjects are randomly selected. For 12 months following the dose, the scientists will conduct follow up examinations.

No serious adverse events directly related to the stem cell therapy were observed in an earlier study. Researchers are encouraged by these reports indicating that the treatment is well-tolerated. Improved exercise capacity and reduced chest pain during the early stages of the trial were reported by 16 of the 24 patients in the Phase I study.