Adult stem cells may reduce damage following heart attack

March 29, 2001

New York, NY, March 30, 2001--Researchers from Columbia University College of Physicians & Surgeons have developed an experimental treatment that, in rats, dramatically improves the recovery prospects after heart attack, using stem cells from human adults. The discovery, published in the April 1 issue of Nature Medicine, may lead to new clues for treatments of heart disease, the foremost killer of people in the industrialized world.

The therapy spurs new blood vessel development in heart tissue following a heart attack, preventing the tissue starvation and death that typically causes heart failure.

Dr. Silviu Itescu, M.D., lead author, researcher and faculty member at Columbia University College of Physicians & Surgeons and director of transplantation immunology at Columbia Presbyterian Medical Center of NewYork-Presbyterian Hospital, and colleagues identified a type of stem cell, present in adult human bone marrow, capable of blood vessel development. The researchers injected these cells into rats that had suffered heart attacks two days earlier. The cells went exclusively to the damaged heart tissue, where they triggered the formation of new blood vessels.

This largely fixed a problem that usually follows a heart attack. "The heart muscle itself is able to compensate for the initial loss in heart tissue by increasing in size following a heart attack," Dr. Itescu said. "For every cell lost after the initial heart attack, others enlarge and take over its function, a process termed compensatory hypertrophy. However, the heart can't develop an adequate blood vessel network to nourish these larger cells. Consequently they die, leading to further heart muscle loss, its replacement with fibrous [scar] tissue, and eventually heart failure and death."

The researchers hypothesized, and showed, that the enlarged heart muscle cells require more oxygen. "If you don't supply them with more oxygen and nutrients, they starve to death," Dr. Itescu said.

The new experimental treatment gets to the core of the problem by helping to ensure that the enlarged, but still viable, heart cells are nourished. This keeps them from undergoing apoptosis, a type of cellular "suicide" or programmed cell death, which leads to conversion of heart muscle into non-functional fibrous or scar tissue.

The researchers began by reviewing developmental medical literature on stem cells, which shows that a type of stem cell called an angioblast is largely responsible for developing the fetal vascular system. The researchers identified a similar type of cell, present in tiny amounts in adult human bone marrow. They extracted, purified and multiplied these human cells in the laboratory, then injected them into the tails of rats that had been induced to have heart attacks two days earlier.

The angioblasts found their way to the damaged heart tissue because this tissue produces special signals, called chemotactic ligands, which the angioblasts recognize through receptors on their surfaces. The angioblasts homed to the damaged area and started producing new vessel networks. They also spurred the development of the rat's own vessels in the immediate vicinity, probably by releasing additional chemicals called trophic factors, Dr. Itescu said.

Adults probably already have a system that partially replicates this process of using angioblasts to help repair damaged heart tissue, but it is inadequate, Dr. Itescu explained. The experimental treatment gives the system a concerted boost.

The treatment led to sustained improvements in heart function of between 30 percent and 40 percent in the rats compared with untreated rats. This assessment was based on widely accepted tests of heart function, such as ejection fraction, which measure the efficiency of the pumping action.

These improvements were sustained throughout the four months of the experiment. In addition, the rats treated with the stem cells developed less than one-third the amount of heart scar tissue compared with the untreated animals, Dr. Itescu noted.

The rats didn't reject the human cells and tissue because their own immune systems had been disabled. The use of human cells, rather than rat cells, was a shortcut the researchers took to bring the procedure that much closer to human trials, Dr. Itescu said.

However, there are obstacles to human trials. For instance, it takes several days to culture the cells to quantities large enough to be useful, which ordinarily would make it difficult to treat humans within the same two-day time spans as the rats in this study.

Dr. Itescu said the treatment might still be beneficial if initiated a few days after the heart attack, but the precise window needs to be defined.

One possible approach, Dr. Itescu adds, "is to store the stem cells of high-risk patients in a blood bank for immediate use when required as the patient develops a heart attack."
-end-
The study was funded by Department of Surgery Columbia University College of Physicians & Surgeons.

Columbia University Medical Center

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