Researchers have healed injured hearts of living mice by reactivating long dormant molecular machinery found in the animals' cells.
The study by Salk Institute that could help pave the way to new therapies for heart disorders in humans suggests although adult mammals don't normally regenerate damaged tissue, they may retain a latent ability as a holdover from development like their distant ancestors on the evolutionary tree.
When the Salk researchers blocked four molecules thought to suppress these programs for regenerating organs, they saw a drastic improvement in heart regeneration and healing in the mice.
Study's senior author Juan Carlos Izpisua Belmonte, a professor in the Gene Expression Laboratory at Salk said that organ regeneration is a fascinating phenomenon that seemingly recapitulates the processes observed during development. However, despite their current understanding of how embryogenesis and development proceeds, the mechanisms preventing regeneration in adult mammals have remained elusive.
Their studies uncovered four molecules in particular-MiR-99, MiR-100, Let-7a and Let-7c-that fit their criteria. All were heavily repressed during heart injury in zebrafish and they were also present in rats, mice and humans.
However, in studies of mammalian cells in a culture dish and studies of living mice with heart damage, the group saw that the levels of these molecules were high in adults and did not decline with injury. So the team used adeno-associated viruses specific for the heart to target each of those four microRNAs, suppressing their levels experimentally.
Injecting the inhibitors into the hearts of mice that had suffered a heart attack triggered the regeneration of cardiac cells, improving numerous physical and functional aspects of the heart, such as the thickness of its walls and its ability to pump blood.
The scarring caused by the heart attack was much reduced with treatment compared to controls, the researchers found and the improvements were still obvious three and six months after treatment-a long time in a mouse's life.
The study was published in the journal Cell Stem Cell.
