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.
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.
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.
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.
this new idea appears to offer a much more elegant solution.
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.
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
the seven guinea pigs treated, five eventually developed heartbeats that were
being driven by their new biologically endowed pacemaker.
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.
by avoiding the use of embryonic stem cells to derive pacemaker cells, the
researchers have reduced the risk of cancerous cells emerging.
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.
the entire study online at Nature Biotechnology.