Sudden Heart Attack Deaths Could Be Slashed By Transplanting GM Cells

by Medindia Content Team on  December 7, 2007 at 6:56 PM Genetics & Stem Cells News   - G J E 4
Grafting gene-altered cells onto cardiac tissue damaged by a heart attack dramatically reduces the risk of sudden death in mice and could one day do the same for humans, said a study released Wednesday.
Sudden Heart Attack Deaths Could  Be Slashed  By Transplanting GM Cells
Sudden Heart Attack Deaths Could Be Slashed By Transplanting GM Cells

One in seven heart attack victims die abruptly within three years, mostly from a condition known as arrhythmia, an irregular -- and in most cases overly rapid -- beating of the heart, said University of Bonn researcher Bernd Fleischmann, who led the study.

In Germany, some 60,000 to 80,000 people experience this kind of "sudden cardiac death" every year, he told AFP.

But a new technique that implants genetically-modified tissue directly into a damaged heart virtually erased the additional risk of arrhythmia in mice that had experienced heart attacks as compared to mice who had not, the study found.

Human heart attack sufferers are frequently fitted with surgically implanted pacemakers designed to deliver electrical impulses to help restore normal rhythm if the heart begins to go haywire.

"But they have a downside," said Michael Kotlikoff of Cornell University, New York, one of the study's co-authors.

"There is no cellular basis for correcting this vulnerability to arrhythmia," he told AFP in a phone interview.

In experiments designed to find such a cell-based solution, Fleischmann and his colleagues transplanted mouse embryo heart cells, called cardiomyocytes, into the hearts of mice that had been induced to have cardiac failure.

"We then directly introduced a catheter into the mouse heart to see whether we could provoke arrhythmia," Fleischmann explained.

The results, published in the British journal Nature, were nothing short of dramatic: the rate of irregular heart activity was the same as with healthy rodents, just over 30 percent.

By contrast, almost 100 percent of a control group of mice which had had heart attacks died when subjected to the same test.

But there was a problem. Taking heart cells from embryos was feasible in laboratory mice, but unthinkable in humans.

Looking for a substitute that might one day work in people, the researchers performed the same heart operation by grafting skeletal muscular cells taken from the leg of the same animal.

Not only did these new cells fail to protect the heart, they actually made the arrhythmia worse.

The difference, Fleischmann realised, "is that heart muscle electrically couples (with the heart tissue), and skeletal muscle does not."

"This electrical coupling occurs because of a protein called connexin 43," found only in heart cells, he said.

It was this discovery that spawned the idea that holds such promise for heart-attack victims living under the shadow of sudden death. The researchers created a line of mice that "over expressed" connexin 43 in skeletal muscle, and repeated the experiment.

This time, it worked as well as with the embryo heart muscle.

"What is key here is that the cells engrafted into the heart are actually connected to the normal heart cells and activated during the normal beat," said Kotlikoff.

Fleischmann said this could open the way to easy and rapid laboratory production of muscle tissue containing connexin 43.

"You can, so to speak, grow tons of muscle. So one approach would be to do ex-vivo gene therapy," he said, referring to a method of nurturing cells in a lab dish and then transplanting them into the patient.

But the researchers cautioned that there were still many key steps to be taken before the therapy could be tested in humans.

It first needs to be tested in large animals, whose hearts differ significantly from those of mice, they said.

Source: AFP

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