Our heartbeats are triggered by a steady stream of electrical signals, which cause our heart muscles to contract with a regular rhythm. For some people, however, the ‘pacemaker cells' responsible for generating these pulses can fail, resulting in an erratic heartbeat. Normally, this problem is addressed by surgery and the insertion of an electric pacemaker device. But as a recent breakthrough at Cedars-Sinai Heart Institute now shows, it may be possible to convert ordinary heart cells into genuine pacemaker cells — and it can be done with a known gene and a modified virus.
There are fewer than 10,000 pacemaker cells in the heart (out of billions of other heart cells) — an astoundingly small number considering how important they are to critical biological function.
Worse, as age and disease takes its toll on the heart, these cells — also referred to as SAN cells (as they are clustered in the sinoatrial node (SAN) of the heart's right upper chamber) — start to degrade, which can result in a cardiac arrest.
Pacemakers certainly provide a viable solution to the problem, but they're clunky, they break easily, they often lead to infections, and they're limited by their finite battery life.
But this new idea appears to offer a much more elegant solution.
Researchers Nidhi Kapoor, Hee Cheol Cho, and their colleagues injected a genetically-modified virus carrying the crucial Tbx18 gene into guinea pigs. This caused ordinary heart cells to transform into the SAN cells; once infected, the heart cells became smaller, thin, and tapered, thus acquiring the exact characteristics of the pacemaker cells.
Tbx18 is the gene that's responsible for pacemaker cell development during the embryonic stage of development. But in this context, the gene directly reprogrammed the pre-existing heart muscle cells (cardiomyocytes) to the SAN cells.
Of the seven guinea pigs treated, five eventually developed heartbeats that were being driven by their new biologically-endowed pacemaker.
Biological pacemakers have been created before, but this is the first time that a single gene was shown to directly convert the heart muscle cells to pacemaker cells. And in fact, the new cells — redubbed iSAN cells (induced SAN cells) — were indistinguishable from native pacemaker cells. Previous attempts resulted in cells that were not true pacemaker cells.
Moreover, by avoiding the use of embryonic stem cells to derive pacemaker cells, the researchers have reduced the risk of cancerous cells emerging.
Once safety and efficacy can be proven in humans, the therapy will likely involve a direct injection of the virus into the patient's heart, or through the creation of pacemaker cells in the lab for eventual transplantation.
Read the entire study online at Nature Biotechnology.
Top image: CLIPAREA l Custom media/shutterstock. Other image: Cedars-Sinai.