Cellular Pacemakers

Researchers have found that by reprogramming cells in pig hearts, it's possible to regulate heart rhythm without a mechanical pacemaker. With further development and human study, it’s possible that for some people, this simple technique could supplement or even replace a pacemaker.

In a study published earlier this week in Science Translational Medicine, researchers from Cedars-Sinai Heart Institute in Los Angeles reported the results of a dozen years of study on biological pacemakers. Although the first human clinical trial is about three years away, this animal study is an important step toward biological treatments for heart rhythm disorders.

Surgically implanted pacemakers are used to treat arrhythmias, or irregular heartbeats, and in the U.S., nearly 300,000 people receive a pacemaker each year. An implanted pacemaker device carries several risks of side effects, such as infection, bleeding, and bruising. Pacemakers must also be surgically removed every so often in order to replace their batteries.

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“Problems with electronic pacemakers include malfunction from hardware, infections, [and] lack of physiological response to exercise,” said study co-author Dr. Eugenio Cingolani, director of the Cardiogenetics-Familial Arrhythmia Clinic at Cedars-Sinai. “Also, they represent a problem in the pediatric population, requiring multiple generator changes due to development, [or] growth,” he said. With a biological pacemaker, some of those complications may not be an issue.

Of the billions of cells in the heart, only 10,000 are sinoatrial node, or “pacemaker,” cells. A gene called T-box 18 (TBX18) naturally causes cells in the sinoatrial node to beat. 

Researchers studied 12 pigs with a condition known as “complete heart block,” in which messages from the sinoatrial node cannot reach the rest of the heart. TBX18 was injected into seven of the pigs' hearts, and it reprogrammed normal heart cells into biological pacemaker cells that could do the work of the blocked sinoatrial node cells.

“TBX18 is a single gene that converts ordinary heart cells into pacemaker cells. In other words, recreates your own pacemaker cells,” Cingolani said.

Two days after they were injected with TBX18, the pigs' hearts began to beat more normally. The restored heartbeat lasted for about two weeks. The pigs that received TBX18 had a much fast heart rate than the pigs with "complete heart block" who were not treated with the gene. Researchers noticed no local or systemic safety concerns during the study.

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Cingolani said his team was surprised that a single gene could convert normal working heart cells into pacemaker cells through a minimally invasive, catheter-based technique. Surgeries to implant traditional pacemakers are becoming less invasive, but still typically require incisions to the chest.

Heart rhythm disorders like sinus node dysfunction and complete heart block are common reasons why patients need pacemakers, he said. With further study, it’s possible that biological pacemaker treatments could also be used for other conditions.

“While the present work tested the biological pacemaker in complete heart block, this therapy could potentially be used to treat other conditions such as sinus node disease, congenital heart block, etc.,” Cingolani said.

Longer-term safety and efficacy studies must be done before human trials can begin, Cingolani said. Even after human clinical trials, the technique must still be approved by regulators before it can be used by cardiologists.

This is not the only investigation into biologic pacemakers. Other researchers have used stem cells to generate heart cells, and in 2012, the Cedars-Sinai researchers studied the effects of TBX18 on guinea pigs.

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