In guinea pig experiments, Johns Hopkins scientists fused common connective tissue cells taken from lungs with heart muscle cells to create a safe and effective biological pacemaker whose cells can fire on their own and naturally regulate the muscle's rhythmic beat.
"This work with fibroblasts could pave the way to an alternative to implanted electronic pacemakers," says Eduardo Marbán, M.D., Ph.D., professor and chief of cardiology at Hopkins and its Heart Institute. "Such a 'biopacemaker' is a potentially important option for patients at too high a risk for infection or who are physically too small to accommodate mechanical pacemakers."
Two sets of tiny electroactive "pacing cells" give rise to the heart's normal rhythm by stimulating other cells to contract in certain sequences. Potentially fatal arrythmias occur when these pacing cells are damaged or die, and implanted pacers have been lifesaving for the estimated 250,000 Americans a year who can tolerate them.
The Hopkins findings, to be presented Nov. 16 at the American Heart Association's annual Scientific Sessions in Dallas, are among several approaches scientists are taking to develop biopacemakers. What makes the Hopkins approach stand out, says Hee Cheol Cho, Ph.D., a postdoctoral cardiology research fellow at Hopkins, is that the fibroblasts are found throughout the body, even in skin. "They proliferate well and grow fast and when fused with heart muscle, form cells that are very stable. Thus, our method would seem to the safest and most convenient so far," he says.
Other biopacemaker technologies, Cho notes, use adenoviruses as part of gene therapy to carry pacing genes into the heart, or use combinations of gene- and stem-cell therapies that may cause cardiac inflammation or uncontrolled cell growth that cause arrhythmias instead of stopping them.
"It is very difficult to guide stem cells into forming exactly the kind of cell needed, but not so with fibroblasts," he says.
In his guinea pig studies, Cho, along with others at Hopkins, successfully combined regular heart muscle cells having no pacing abilities with fibroblasts taken from the animals' lungs. The fibroblasts had been altered by adding HCN1, a gene that codes for potassium ion channels, and another gene, If, which produces proteins involved in electrical signaling, called pacemaker channels. Such channels are protein structures that permit electrical signals, the ions, to pass in and out of cells.
Within three minutes of fusion, the cells showed signs of forming their own potassium ion channels and began generating their very own electrical current, one much like the heart's natural pacing cells would. The effect lasted at least two weeks. The team also fused heart muscle cells with control fibroblasts that had not been genetically altered, but no pacemaker activity developed.