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Stem Cell Study Raises More Questions about Therapies
By Nancy Touchette

Bone marrow stem cells fuse with liver cells in mice to produce a hybrid cell (blue) that contains two nuclei.

The seemingly remarkable ability of stem cells to turn into other types of cells has fueled research on experimental therapies, particularly involving stem cells isolated from a person's bone marrow.

A boy in Michigan received injections of his own bone marrow stem cells in February 2003 to repair his damaged heart, and his condition reportedly improved. Clinical trials are planned or underway in several countries to test whether bone marrow stem cells can help patients with heart disease.

But some researchers have challenged the claim that bone marrow stem cells are actually becoming other cells. They say these cells are “fusing” with other cells rather than actually changing their genetic program, and a major study published in May 2003 reported that bone marrow stem cells had fused with liver cells in mice.

Now a new study weighs in with similar findings, showing that bone marrow stem cells transplanted in mice fused with liver cells, neurons and heart cells. Fusion occurs when a bone marrow cell somehow adheres to another cell. The membranes join and the resulting cell has two nuclei and double the number of chromosomes

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This is what concerns some researchers. They argue that because fused cells contain an abnormal number of chromosomes, they could lead to cancer or other problems.

But it's also possible that cell fusion is a naturally occurring process that plays a role repairing tissues. At the moment, no one is sure just what's going on.

Until researchers fully understand how bone marrow cells restore damaged tissues, clinical applications should be put on hold, says Arturo Alvarez-Buylla of the University of California, San Francisco, who led the new study of bone marrow stem cells in mice.

His team transplanted bone marrow stem cells into mice. Two months later, the bone marrow cells had fused with cells in the brain, the liver, and the heart. The researchers did not find evidence, however, of fusion with other cells.

Alvarez-Buylla and his colleagues would like to know which cells are doing the fusing—and why some cells and not others appear to fuse with bone marrow cells. They would also like to know whether cell fusion is normal or not.

“It's not so important to point a finger at who is right and who is wrong, but it is important to find out what is really going on,” says Alvarez-Buylla.

“If fusion is a mistake of cell biology and cells end up getting stuck together, this could interfere with normal cell function,” he says. “Until we know what's going on it's too much of a risk for the patient.”

The confusion over whether bone marrow cells fuse with other cells has prompted some researchers to move away from the idea of using these cells to repair damaged tissues.

For example, Piero Anversa, of the New York Medical College in Valhalla first discovered that bone marrow stem cells could repair damaged heart cells in mice. But he has since abandoned this work and focused on cardiac stem cells. His team recently discovered stem cells in cardiac tissue in humans and rats.

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M. Alvarez-Dolado et al. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature, published online October 12, 2003.


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