In
an embryo the cells help build the heart, but in adulthood they
generally go dormant, said researcher Paul Riley of the Institute of
Child Health in London. The new study found a way to reactivate them, he
said.
The
findings suggest that someday it might be possible to develop a drug
for at-risk people to keep those dormant cells ready in case of a heart
attack, said Riley, an author of the report in Thursday’s issue of the
journal Nature. But that would be at least 10 years away, he stressed.
The
cells are found in the outer layer of the mouse heart. Researchers
found that if they injected mice with a particular substance and gave
the animals a heart attack, the cells migrated to the site of injury and
made new muscle. They also found several indicators that the heart then
worked better, although they said it’s not clear whether that’s due to
the new muscle or other known effects of the injected substance.
Steve
Houser, director of the Cardiovascular Research Center at Temple
University, who wasn’t involved in the study, said other teams have also
reported potential repair cells in the heart, including some cells
being tested in humans.
He also cautioned that “very little in the cardiac world has translated from mice to man.”
Yet, he said the new research was well done and will “stir the field” of heart regeneration studies.
Researchers
have for the first time succeeded in transforming a new type of
stem-like cell in the adult heart, into heart muscle in mice. The study,
led by UCL scientists and published online in Nature, proves the heart
has dormant repair cells in its outer layer that may be re-activated.
The research suggests that in the future hearts damaged by a heart
attack could be encouraged to repair themselves.
The
damage caused by a heart attack is currently permanent. It can lead to
heart failure, which is debilitating, has a poor prognosis, and affects
over 750,000 people in the UK.
British
Heart Foundation-funded scientists working at UCL targeted stem-like
cells called progenitor cells in the epicardium, the outer layer of the
heart. In the embryo, these epicardium-derived progenitor cells (EPDCs)
are able to transform into a number of specialist cells including heart
muscle. Scientists thought this ability was lost in adults but
researchers have managed to reactivate this potential.
They
restored the EPDCs’ embryonic potential by treating the healthy hearts
of adult mice with a peptide molecule called thymosin ?4 (T?4). This
appeared to ’prime’ the heart for repair. When damage to the heart
occurred, a booster dose of T?4 was given, and this sparked the EPDCs to
transform into new heart muscle and integrate with existing healthy
muscle. Crucially, muscle is not formed if the EPDCs have not been
pre-treated with T?4.
Explaining
how this work might eventually translate into clinical practice,
Professor Paul Riley (UCL Institute of Child Health), who led the
research, said: “I could envisage a patient known to be at risk of a
heart attack – either because of family history or warning signs spotted
by their GP – taking an oral tablet, along the lines of a statin, which
would prime their heart so that if they had a heart attack, the damage
could be repaired.”
However,
treatments based on this method are several years away. T?4 enabled
only a limited number of heart muscle cells to be generated. With BHF
funding, the researchers now plan to carry out further research into the
molecule. They hope to make it more effective or come up with
alternative ways to activate the embryonic potential of EPDCs and
eventually translate what they have found in mice into humans. This will
also be helped by gaining better knowledge of the mechanism by which
T?4 works.
Professor
Riley added: “This is an important piece of work and something we’ve
been working toward for some time. Our earlier research proved blood
vessels could be regenerated in adult hearts but there were major doubts
about whether the same might be true for heart muscle. This work has
demonstrated a possible method for repairing hearts damaged by a heart
attack and could have a major impact on future therapies to treat heart
failure.”
Professor Jeremy Pearson, Associate Medical Director at the BHF, said:
“To
repair a damaged heart is one of the holy grails of heart research.
This groundbreaking study shows that adult hearts contain cells that,
given the right stimulus, can mobilize and turn into new heart cells
that might repair a damaged heart. The team has identified the crucial
molecular signals needed to make this happen.
“These
results strengthen the evidence that in the future there may be a drug,
or cocktail of drugs, that could be given to people whose hearts have
been damaged by a heart attack, to prevent the onset of heart failure.
This is why the BHF has launched its Mending Broken Hearts appeal to
raise money for research to turn this vision into reality for heart
patients as quickly as possible.”
Source: University College London