Cardiac regeneration  pg. 2

Excitement began to build in the late 1990s, when several laboratories independently reported that circulating stem cells derived from bone marrow could differentiate into many different types of tissue cells, including the endothelial cells that line blood vessels.

Mounting evidence

Recent studies in animals have buoyed the promise of stem cell therapy for heart repair.

In a 2001 study, researchers treated mice with their own bone marrow-derived stem cells following an experimentally induced heart attack. Injection of these cells into the damaged heart tissue improved survival and led to the formation of new cardiomyocytes, vascular endothelium and smooth muscle cells, the investigators found.

“There was also clinical evidence,” says Hatzopoulos, noting earlier clinical observations of tissue regeneration in people who had previously received bone marrow transplants.

“If you look at a biopsy, you find that some of the cells that are part of the new tissue are coming from the donor (bone marrow)… indicating that there is a low level of wear and tear and replacement, and that bone marrow stem cells seem to be part of it.”

The mounting evidence triggered a number of clinical trials outside the United States—even while basic scientists were still conducting studies in animal models.

The clinical trials, which have used bone marrow-derived stem cells injected five to eight days after heart attack, have demonstrated that such therapies are safe and may offer a “moderate” improvement in heart function.

Among patients who received the cells, researchers observed an increase in the left ventricular ejection fraction (a measure of how efficiently the heart pumps blood), a reduction in the size of the infarct (indicating that the damaged heart muscle was being repaired), and an improved ability to exercise.

With these promising results, the National Heart, Lung, and Blood Institute in 2006 established a network of clinical centers to investigate this heart repair strategy in a more systematic way. Vanderbilt University Medical Center was among the network’s five founding centers—along with the Texas Heart Institute, the University of Florida, the Cleveland Clinic and the University of Minnesota.

Vanderbilt also recently enrolled its first subjects into a privately-funded study (see “Stem cell pioneer”).

Despite the promising results from the clinical trials completed to date, the clinical benefit seems modest, suggesting that the therapy has much room for improvement. So researchers are heading back to the bench.

Says Hatzopoulos: “I think the key questions in the field are: which is the best cell type, how do we get the cells to go to the desired site efficiently, how can we enhance their survival in a hostile environment, and how do we direct them into becoming the tissue cells we want?”

While bone marrow is an easily accessible and abundant source of cells, the majority of bone marrow stem cells are ultimately destined to become blood cells. A small percentage of these cells appear to develop into cardiomyocytes, but Hatzopoulos says they may require an extensive “re-education” to produce numbers adequate for significant heart repair.

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