Winter 2007

Stem Cells May Repair Injured Myocardium

In the last two decades, a number of new therapies have dramatically improved survival and quality of life for heart attack patients. After a heart attack, loss of contracting heart muscle cells occurs, resulting in scar formation and subsequent heart failure.

Current therapies designed to treat heart attack patients in the acute setting include medical therapies and catheter-based technologies that aim to open the blocked coronary arteries with the hope of salvaging as many of the jeopardized heart muscle cells as possible.

Unfortunately, despite these advances, it is rarely possible to rescue the at-risk heart muscle cells from some degree of irreversible injury and death. In addition, the delay in time until most patients present to receive their care has been recognized as a major factor in the failure of current techniques in preventing significant cardiomyocyte injury. Yet none of these technologies regenerate the heart muscle cells that are injured or have died after a heart attack.

Attention has turned to new methods of treating heart attack and heart failure patients in both the acute and chronic settings after their event. Heart transplantation remains the ultimate approach to treating end-stage heart failure patients. But this therapy is invasive and costly, some patients are not candidates for transplantation given their other comorbidities and, most important, there are not enough organs for transplanting the increasing number of patients who need this therapy.

Newer therapies are needed to treat the millions of patients with debilitating heart conditions. Recently, it has been discovered that stem cells, which are early progenitor cells with the ability to direct the production of all the different types of human cells, may hold the therapeutic potential for these patients.

Experimental studies in both animals and humans have revealed encouraging results when stem cells were injected into the heart in the areas of myocardial infarction. These therapies appear to result in improvement in the contractile function of the heart.

UCSF interventional cardiologist and researcher Yerem Yeghiazarians, M.D., hopes that stem cells may offer a way to repair damage to the heart that results from heart attack.

"About five years ago, initial, promising work showed that when directly delivered to the heart, bone marrow stem cells may have the potential to improve the heart function after a heart attack," Yeghiazarians says. "Experiments and larger clinical trials have since shown that such autologous stem cell transplantations may be effective in repairing the heart function. But the results have thus far been mixed, and many questions remain to be answered."

These findings are only the beginning of a journey to the development of an effective therapy, Yeghiazarians says. To create a dependable therapy, a lot of research lies ahead.

"We don't really know yet what the mechanisms are for some of the improvements in the heart function after cell-based therapy," Yeghiazarians says. "It has been proposed by some that the stem cells may integrate themselves into the heart and differentiate into myocytes or even fuse with the existing cardiomyocytes. But more likely, the stem cells appear to act like a factory with the ability to release proteins or other growth factors that help the existing tissue heal."

In addition, clinical researchers don't know yet the best way of delivering the stem cells to take up residence in the heart. "One technique is to directly inject the stem cells into the heart muscle. Another is to deliver them inside the main coronary arteries that supply blood to the heart, or to even use chemical factors or signals that guide stem cells circulating in the blood to the heart tissue," Yeghiazarians says.

Ultimately, enhancing the body's own repair mechanisms may prove the most effective mode of therapy, Yeghiazarians says. "We know that after a heart attack, there is an increased number of stem cells circulating in the blood," he says. "One of our many interests is to find out how these stem cells are mobilized and guided to the heart."

Yeghiazarians and his colleagues are also interested in better understanding the role of the stem cells circulating in the blood that may be used for autologous cell transplantation into the heart for cardiac repair.

"Like a lot of things, the circulating stem cells become less effective with age and with increasing cardiovascular risk factors," Yeghiazarians says. "We would like to better understand why the stem cells become less effective in certain medical conditions and figure out how we can make them work better, so they can become more effective as therapeutic agents for cardiac repair."

A related area of interest for Yeghiazarians is native heart progenitor cells. "We used to think that the heart doesn't regenerate itself, but recently we've begun to think that maybe it does," he says. There appear to be native progenitor cells in the heart that may become active after a heart attack. How to spot these cells and prompt them to repair damaged heart tissue will be an exciting research area in the future.

Yet another area of study is tissue engineering to treat heart attacks. Sheets of such cells may ultimately replace damaged areas of the heart without the need for a full heart transplant. Some researchers believe that it may be possible someday to grow sections of a heart from these cells on a biomechanical scaffold.

Clinical Trials already underway

Currently at UCSF, cardiac stem cell research is actively being pursued in small and large animals, and a number of exciting observational human clinical trials are already underway. "We are very excited about the Cardiac Translational Stem Cell Program at UCSF. In the near future, we hope to begin cell-based therapies in our patients who have suffered a major heart attack to improve their heart function," Yeghiazarians says.

When such clinical trials start, Yeghiazarians and his research team will be looking for patients at UCSF and in Northern California who have suffered a significant heart attack to enroll in the trial.

"Cell-based therapies have a bright future," Yeghiazarians says. "We have a lot of different groups collaborating at the university level to push the field forward."

To contact Dr. Yerem Yeghiazarians, call (415) 353-3815.

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