December 17, 2012
Biological Pacemaker Created By Injecting A Single Gene
Brett Smith for redOrbit.com - Your Universe Online
Cardiologists from The Cedars-Sinai Heart Institute in Los Angeles have announced the development of a biologically-based pacemaker by reprogramming ordinary heart cells using the introduction of a single gene - Tbx18.
"Although we and others have created primitive biological pacemakers before, this study is the first to show that a single gene can direct the conversion of heart muscle cells to genuine pacemaker cells. The new cells generated electrical impulses spontaneously and were indistinguishable from native pacemaker cells," said Hee Cheol Cho, PhD., a Cedars-Sinai Heart Institute research scientist.
According to the researchers´ report in Nature Biotechnology, they used a virus to infect heart muscle cells of guinea pigs with Tbx18, which is functioning when pacemaker cells are created during normal embryonic development. After infection, the heart cells became smaller, thinner, and acquired the "distinctive features of pacemaker cells", the report said.
Of the seven guinea pigs used in the experiment, five eventually had heartbeats originating from the new pacemaker cells.
"The new cells generated electrical impulses spontaneously and were indistinguishable from native pacemaker cells," Cho told the AFP news agency in an email statement. "We expect this to work in humans. It would be two to three years from now until the first clinical trial, the first target patients being the ones with (pacemaker) device infection.”
A heartbeat begins in the sinoatrial node (SAN), located in the heart's right upper chamber. The fewer than 10,000 pacemaker, or SAN, cells found there are just a fraction of the heart´s 10 billion cells.
Once the cardiologists were able to reprogram the rodent SAN cells, they adopted all of the function of naturally occurring pacemakers and maintained this functionality even after the effects of the Tbx18 gene were no longer observed.
“This is the culmination of 10 years of work in our laboratory to build a biological pacemaker as an alternative to electronic pacing devices,” said Eduardo Marban, director of the institute.
Most patients currently rely on electronic pacemakers to treat their irregular heartbeat and these devices are susceptible to breakage or damaged wires that connect to the heart. Electronic pacemakers also contain batteries that must be periodically replaced.
“All these problems could be solved by a biological pacemaker, which is microscopic in scale and free of all hardware,” Cho told BBC News.
Cho compared the use of electronic pacemakers to attaching an electronic motor to a bicycle. While the need to pedal such a contraption is removed, the vehicle is still a bicycle.
“In this study, we discovered that this gene could reprogram all major parts of the heart muscle cells to those of native pacemaker cells,” Cho told Bloomberg. “The bicycle transformed into a Harley.”
Previous research to create a biologically-based pacemaker has resulted in heart muscle cells that could beat on their own, but the modified cells were more like muscle cells than true pacemakers. While some approaches used embryonic stem cells, the specter of cancerous cells loomed large over these techniques. This latest study accomplishes the creation of new pacemaker cells, but without the risk of cancer.