Embryonic Stem Cells Keep Heart Beating

They acted like pacemaker in animal trials

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HealthDay Reporter

MONDAY, Dec. 20, 2004 (HealthDayNews) -- Researchers say they have transformed embryonic stem cells into heart cells that could someday replace the electronic pacemakers now implanted to keep hearts beating normally.

"By transplanting these human heart cells into the ventricle [heart chamber] of an animal, we can make them beat spontaneously," said Ronald Li, an assistant professor of medicine at Johns Hopkins Medical School and leader of the group reporting the work in the Dec. 20 online issue of Circulation. "The implication is that eventually we could make a biological pacemaker to replace electronic pacemakers."

The Hopkins work avoids the controversy over the use of human stem cells because it was done with a line of embryonic stem cells, designated ES, grown at the University of Wisconsin, one of the few lines approved for use by the Bush administration.

While the results look good, "we need to be very careful in terms of launching human trials," Li said.

Experiments have been done in guinea pigs, and the work needs to be repeated in large animals such as pigs, whose hearts are more similar to those of humans, he said. The implants must be followed for a prolonged period, to be sure that they will not turn cancerous or be attacked by the immune system, Li said.

"So far, we have not seen rejection or tumor formation, but we have to do prolonged experiments to be sure," he said.

A first step in the research was to insert a gene into the embryonic cells that would make them produce a fluorescent green protein, so that they could easily be distinguished from animal cells. That was done by Tian Xue, a postdoctoral fellow.

The glowing cells were then given treatment to transform them into heart cells. The researchers then selected clusters of the cells that were beating on their own and implanted them in the hearts of guinea pigs.

The animals' own pacemaking cells were destroyed by freezing a few days later. Electrical measurements showed a new beat, coordinated by the implanted cells, at a rate slower than the animals' normal beat and closer to that of the human heart.

Studies then confirmed that the electrical signals controlling the heartbeat originated in the implanted cells.

Genetic engineering techniques now are being used to adjust the pacing rate of the cells, so that they would be appropriate for use in the human heart, Xue said.

Most efforts on stem cell therapy for the heart have used adult stem cells, generally from the bone marrow, whose ability to be transformed into other cell types is more limited than is true of embryonic cells. The U.S. Food and Drug Administration earlier this year approved the first clinical trial of such therapy by the Texas Heart Institute.

But recent reports have not been encouraging. Researchers at the University of Chicago have just reported that while the bone marrow stem cells migrate into the heart, they do not mature into new cardiac muscle cells. A similar disappointment was reported earlier this year by Swedish researchers at Lund University.

More information

Learn the basics of stem cell therapy from the National Institutes of Health.

SOURCES: Ronald Li, Ph.D, assistant professor, medicine, Johns Hopkins Medical School, Baltimore; Dec. 20, 2004, Circulation online

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