Adult stem cell therapy for heart failure proves promising

November 11, 2000

A new stem cell technique holds exciting potential for treating life-threatening heart failure, Canadian researchers reported today at the American Heart Association's Scientific Sessions 2000.

The approach involves taking mature stem cells from an animal's own bone marrow and injecting them directly into the heart. These cells, called marrow stromal cells, then change, or differentiate, into heart muscle cells.

So far, these experiments have only been done in animals. The Canadian team reported it had successfully created viable new heart muscle in 20 of 22 rats treated.

"Heart failure is the death of functioning heart muscle," says senior author Ray C. J. Chiu, M.D., Ph.D., professor and chairman of the division of cardiothoracic surgery at McGill University Health Centre in Montreal. "The goal of our study is to replace those dead cells with new heart muscle cells. Marrow stromal cells are extremely promising."

At birth, humans have all the heart muscle cells they will ever develop. Unlike many tissues in the body, heart muscle cells cannot replace themselves, and instead of adding new cells, the heart grows after birth by enlarging the cells it has.

"When heart cells die, they are permanently lost," Chiu says.

Heart failure stems from damage to the heart that leaves it unable to pump enough blood to meet the body's needs. It can result from a heart attack, viral infection of the muscle, or an inherited heart defect.

One way to possibly replace dead heart muscle would be the use of embryonic stem cells. These early cells can differentiate into any cell type, given the proper signal in the body, but harvesting them destroys the embryo.

The new therapy being pursued by Chiu's group might offer an alternative to using embryonic stem cells. Also, because the marrow stromal cells come from the patient, there would be no rejection of the new muscle by the immune system, thus there would be no need for expensive immunosuppressive drugs, says Chiu.

The technique, which other research teams are investigating for treating diseases affecting several organs, emerged from decades of basic research.

"In the classic view of science, bone marrow had only one function - to replace red cells and white cells in the blood," Chiu explains. "The stromal cells were thought to be there just to support the production of blood cells. Only in the last couple of years did we recognize definitely that these marrow stromal cells are adult stem cells."

In their experiment, Chiu and his colleagues used 22 adult rats with identical genes - which eliminates the threat of rejection. Each of the animals received a single injection of marrow stromal cells into the heart.

To identify the injected cells, so they would know whether the cells survived and became heart muscle, the researchers attached a chemical to them that becomes fluorescent. "We found that the cells survived and looked like heart muscle," Chiu says.

To further identify the presence of heart muscle cells and track the progress of the injected cells, researchers stained cell samples from the rat hearts so that certain heart muscle proteins would show up. That test proved positive. "Four weeks after being injected, the cells had heart muscle protein," Chiu says.

The second protein they stained for is found at a specific junction between two heart muscle cells. That test revealed normal heart muscle side by side with the injected cells that had transformed into heart muscle. "If the two were not connected, this protein would not develop and such connections are important for them to beat together," he notes.

He and his colleagues made another intriguing finding. Two groups of cells were produced from the injected marrow stromal cells. When the second population of cells, which spread from the injection site, came into contact with muscle cells, they also grew into muscle cells. However, some cells remained in the tiny needle hole and became trapped by scar tissue. These cells did not grow well. At 12 weeks, the team found evidence of the protein involved in heart muscle contraction, but the trapped cells did not look like muscle.

"The message we are getting is that for these stromal cells to become muscle, they need very close contact with muscle cells and some sort of signal that tells them how to differentiate," Chiu says. "We don't know what that signal is and further study is needed to identify it."
Co-authors are Jih-Shiuan Wang, M.D.; Dominique Shum-Tim, M.D.; Edgar Chedrawy, M.D.; Nicoletta Eliopoulos, Ph.D.; and Jacques Galipeau, M.D.

American Heart Association

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