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Ordinary heart cells become "biological pacemakers" with injection of a single gene

“Although we and others have created primitive biological pacemakers before, this study is the first to show that a single gene — the TBx18 — can direct the conversion of heart muscle cells to genuine pacemaker cells,” said Hee Cheol Cho, Ph.D., a lead researcher on the Cedars-Sinai Heart Institute team that made the discovery. “The new cells generated electrical impulses spontaneously and were indistinguishable from native pacemaker cells.”

Pacemaker cells generate electrical activity that spreads to other heart cells in an orderly pattern to create rhythmic muscle contractions. If the cells go awry, the heart pumps erratically at best and many patients end up needing a pacemaker to survive.

The heartbeat originates in the sinoatrial node (SAN) of the heart’s right upper chamber, where pacemaker cells are clustered. Of the heart’s 10 billion cells, fewer than 10,000 are pacemaker cells, often referred to as SAN cells.

But the Cedars-Sinai researchers, employing a virus engineered to carry a single gene (Tbx18) that plays a key role in embryonic pacemaker cell development, directly reprogrammed heart muscle cells to specialized pacemaker cells. The new cells took on the distinctive features and function of native pacemaker cells, both in lab cell reprogramming and in guinea pig studies. The cells are also free from the risk of developing into tumors.

If subsequent research confirms the findings of the pacemaker cell studies, the researchers believe therapy might be administered by injecting Tbx18 into a patient’s heart or by creating pacemaker cells in the laboratory and transplanting them into the heart. But, they added, additional studies of safety and effectiveness must be conducted before human clinical trials begin.

The study was published online December 16 in Nature Biotechnology.

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Citation: Nature Biotechnology, “Transcription factor-driven conversion of quiescent cardiomyocytes to pacemaker cells,” online Dec. 16, 2012; print publication in issue dated Jan. 8, 2013.