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Newswise LA JOLLAResearchers at the Salk Institute have healed injured hearts of living mice by reactivating long dormant molecular machinery found in the animals cells, a finding that could help pave the way to new therapies for heart disorders in humans.

The new results, published November 6 in the journal Cell Stem Cell, suggest that although adult mammals dont 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.

The findings provide proof-of-concept for a new type of clinical treatment in the fight against heart disease, which kills about 600,000 people each year in the United Statesmore than AIDS and all cancer types combined, according to the U.S. Centers for Disease Control and Prevention.

Organ regeneration is a fascinating phenomenon that seemingly recapitulates the processes observed during development. However, despite our current understanding of how embryogenesis and development proceeds, the mechanisms preventing regeneration in adult mammals have remained elusive, says the studys senior author Juan Carlos Izpisua Belmonte, a professor in the Gene Expression Laboratory at Salk.

Within the genomes of every cell in our bodies, we have what information we need to generate an organ. Izpisua Belmontes group has for many years focused on elucidating the key molecules involved in embryonic development as well as those potentially underlying healing responses in regenerative organisms such as the zebrafish.

Indeed, back in 2003, Izpisua Belmontes laboratory first identified the signals preceding zebrafish heart regeneration. And in a 2010 Nature paper, the researchers described how regeneration occurred in the zebrafish. Rather than stem cells invading injured heart tissue, the cardiac cells themselves were reverting to a precursor-like state (a process called dedifferentiation), which, in turn, allowed them to proliferate in tissue.

Although in theory it might have seemed like the next logical step to ask whether mammals had evolutionarily conserved any of the right molecular players for this kind of regenerative reprogramming, in practice it was a scientific risk, recalls Ignacio Sancho-Martinez, a postdoctoral researcher in Izpisua Belmontes lab.

When you speak about these things, the first thing that comes to peoples minds is that youre crazy, he says. Its a strange sounding idea, since we associate regeneration with salamanders and fish, but not mammals.

Excerpt from:
Salk Scientists Discover a Key to Mending Broken Hearts

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