Scientists have developed a new method that allows for more efficient and more complete reprogramming of skin cells into beating heart cells.
These findings, based on animal models, offer new-found optimism in the hunt for a way to regenerate muscle lost in a heart attack, researchers said.
"Scientists have previously shown that the insertion of between four and seven genetic factors can result in a skin cell being directly reprogrammed into a beating heart cell," said Sheng Ding, the paper's senior author and a professor of pharmaceutical chemistry at the University of California, San Francisco, with which Gladstone Institutes is affiliated.
"But in my lab, we set out to see if we could perform a similar transformation by eliminating - or at least reducing - the reliance on this type of genetic manipulation," Ding said.
The research team used skin cells extracted from adult mice to screen for chemical compounds, so-called 'small molecules', that could replace the genetic factors.
Ding and his research team have previously harnessed the power of small molecules to reprogramme skin cells into neurons and, more recently, insulin-producing pancreas cells.
They reasoned that a similar technique could be used to do the same with heart cells.
"After testing various combinations of small molecules, we narrowed down the list to a four-molecule 'cocktail,' which we called SPCF, that could guide the skin cells into becoming more like heart cells," said Gladstone Postdoctoral Scholar Haixia Wang, the paper's lead author.
"These newly reprogrammed cells exhibited some of the twitching and contracting normally seen in mature heart cells, but the transformation wasn't entirely complete," Wang said.
So Ding and Wang decided to add one genetic factor, called Oct4, to the small molecule cocktail. And by doing so, the research team was able to generate a completely reprogrammed beating heart cell.
"Once we added Oct4 to the mix, we observed clusters of contracting cells after a period of just 20 days," said Ding.
"Remarkably, additional analysis revealed that these cells showed the same patterns of gene activation and electric signalling patterns normally seen in the ventricles of the heart," Ding added.
Ding and his team believe that these results may point to a more desirable method for reprogramming, as ventricular heart cells are the type of cells typically lost during a heart attack.
These findings give the team newfound optimism that the research is well on its way towards an