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Medicine’s Houser thinks stem cells may fight heart failure

Houser
Houser

If you’ve ever used a loofah in the shower, you’ve stirred up some stem cells. As the outer layer of skin sloughs off, stem cells in the dermis rush to repair and replace those buffed away.

Now imagine a tiny loofah that works in much the same way inside the corridors of the human heart. As it scrubs, it alerts heart stem cells to rush to the site of dying cells to begin renewal and repair of cardiomyocytes cells that pump blood through the heart.

While a heart loofah may remain the stuff of medical fantasy, Steven Houser, director of the Cardiovascular Research Center at the School of Medicine, is sold on the idea that the heart like the skin contains its own stem cells: cells that are self-renewing and can be differentiated into different types of heart tissue. It’s a controversial subject in cardiovascular circles, but for Houser, who spent 30 years studying the molecular biology of heart cells, the stakes are worth it when it comes to combating congestive heart failure (CHF).

CHF, which afflicts 4.8 million Americans, occurs when the heart no longer has the strength to pump blood efficiently, resulting in an increasingly diminished quality of life. While a wide variety of well-understood conditions such as high blood pressure or excess weight can lead to CHF, a cure for the debilitating disease is less clear. Invasive surgical procedures such as a bypass operation or the insertion of a stent can extend a patient’s life, but the essential damage to the heart caused by the condition remains. Pharmacological therapies to improve the function of cardiac muscle cells improve heart function, but the treatments often lead to fatal arrhythmias, canceling out any benefits.

To Houser, the problem proved frustrating.

“Cells were dying in the heart, and there were simply not enough new cells to replace them,” he said. “They were tired soldiers who could no longer work efficiently, and there were no new soldiers coming to take their place.”

Although stem cells have been found in many other organs in the body, including the brain, many cardiac researchers remain unconvinced that the heart contains stem cells. Stem cells can reproduce excessively and cause tumors, and the heart rarely gets tumors. This, along with the observation that adult cardiac cells do not have the capacity to proliferate, has led most investigators to accept the dogma that no new cardiac cells are manufactured in the normal heart.

Houser respectfully disagrees. Abandoning his prior cell research, he joined forces with one of the foremost investigators in cardiac stem cells, Pierro Anversa, professor of medicine and director of the Cardiovascular Institute at the New York Medical College at Valhalla. Anversa, who has been on the forefront of stem cell research for the past five years, has suggested that heart cells undergo an ongoing turnover fueled by cardiac stem cells. In June, Anversa published a study that actually identified cardiac stem cells in animal models that repaired tissue damaged by a heart attack.

One element that convinced Houser of Anversa’s work was his own research into how the heart reacts under the stress of hypertensive diseases that can lead to congestive heart failure.

Early in the disease, the heart muscle mass increases and the chambers stretch in a vain attempt to increase contracting power. While part of the enlargement is due to increased muscle mass, the question of how the chambers grow is less certain.

The traditional view holds that cardiac cells simply grow larger to accommodate the increased need, but Houser and Anversa developed a different theory: Spurred by the cardiac stem cells, cardiomyocytes actually increase in number in their response to the heart’s traumatic condition.

“It was striking that with hypertension there were actually more cardiomyocytes than were originally lost,” Houser said. “New myocytes were forming in excess of the cells that were dying.”

And if that were true, these were the new soldiers to replace those missing in action.

To test this theory, Houser, with the help of Anversa, has received a new National Institutes of Health grant to study if there are autologous stem cells in the heart. The two researchers have arrived at a deceptively simple idea. After inducing hypertension in an animal model to produce a distressed heart, they will study the heart tissue and count cells, first in the normal heart and then in a heart that must work harder to develop excess pressure. If, according to the scientists’ thesis, there are more cardiomyocytes in the heart as opposed to simply larger cells, they will conclude that stem cells had a hand in an attempt to repair and restore the heart.

If their hunch proves correct, the implications for treatment of heart disease are profound. In the future, for example, Houser envisions people banking their own stem cells, so that when a problem arises, new tissue can be made by injecting these cells into the damaged heart. The idea is simple: Use the patients’ own cardiac stem cells to repair their damaged hearts.

“We’ve made a tremendous impact on cardiovascular diseases such as congestive heart failure through the hard work of physicians, better service, stents and bypasses,” he said. “But what we need to do now is to reverse this disease rather than just slow its progression.”

Although his colleagues may remain skeptical, Houser has committed himself to the stem cell model. Inducing cells to promote repair can answer the question that has haunted his career.

“We don’t know how to fix the broken heart, but stem cells might be a large part of the answer.”

- By Ilene Raymond

 

 


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