Researchers at the University of California-Davis have successfully restored normal heart rhythms in pigs with electronic pacemakers using a custom designed protein and gene delivery system:
The UC Davis study, which was co-authored by an international team that included scientists from the University of Hong Kong and Johns Hopkins University, is published in the current issue of the journal Circulation…
In the current study, the researchers delivered a gene encoding a bioengineered cell-surface protein to heart muscle cells of pigs. This protein mimics the combined action of several proteins called HCN ion channels, which play a critical role in maintaining a normal, evenly paced heartbeat. These channels control the flow of sodium and potassium ions in and out of cells that regulate the electrical impulses of the heart.
“These channels are critical to normal heart function. We were able to make one protein that codes for a single channel that does the work normally required by several,” Li explained.
By getting heart muscle cells to produce bioengineered HCN channels, Li and his colleagues were able to reconstruct the SA node of the heart in pigs with implanted electronic pacemakers. The SA node is normally located on the right atrium, the upper right chamber of the heart that receives deoxygenated blood from the body.
“We were even able to create new pacemaker regions on the left atrium,” Li said.
According to Li, the current study moves research beyond using animal models such as mice and rats, whose hearts can beat up to 600 times per minute. Large animals such as pigs make for far more realistic models because their anatomy and physiology, including average heart rates of about 70 to 80 beats per minute, are similar to humans.
In the current study, researchers used radiofrequency ablation to remove the SA nodes in pigs’ hearts. This is the same minimally invasive technique cardiologists use in clinics to destroy the heart cells that cause abnormal electrical discharges and rapid heart rates in their patients. To restore the SA node function and evaluate the bioengineered cells, Li’s team then implanted electronic cardiac pacemakers like those used in humans and injected an adenovirus carrying a gene encoding for the engineered HCN protein into the heart muscle. Adenovirus has the ability to deliver its own genes into a host cell and hijack its protein-synthesizing machinery. Scientists use this ability to deliver genes of interest into cells.
In a matter of days following the gene transfer, the pigs’ hearts had generated bioartificial nodes at the injection sites. Li explained that, through gene expression, normal muscle cells of the heart were converted into pacemaker cells by a process called transdifferentiation. Studies done two weeks after the injections showed the new nodes were able to take over pacemaking function from the electronic devices. The results also have implications for future stem cell research.