STEM-CELL RESEARCHERS AT UCLA have revealed why adult human cardiac myocytes – specialized muscle cells in the heart – have lost their ability to proliferate, perhaps explaining why the human heart has little regenerative capacity.
The study, done in cell lines and mice, may lead to methods of reprogramming a patient’s own cardiac myocytes to create new muscle to repair damage, says Robb MacLellan, M.D., a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
Unlike newts and salamanders, for example, human adults cannot spontaneously regrow damaged organs. Recent research, however, suggests that mammals do have the ability to regenerate heart muscle, but only for a very brief period, during about the first week of life.
If we had it once, Dr. MacLellan reasons, maybe it is possible to regain that ability. The study, published in Cell Biology, suggests it might be possible to turn back the cellular clock to a time when cardiac myocytes had the ability to proliferate and regrow heart muscle.
“These salamanders and other lower organisms have the ability to de-differentiate cardiac myocytes, or take them back to an earlier, more primitive state, which allows them to reenter the cell cycle, creating new heart muscle,” says Dr. MacLellan. “In mammals, we’ve lost that potential. If we knew how to restore that, or knew the reason why adult myocytes can’t do it, we could try to figure out a way to use nature’s methods to regenerate the heart.”
Dr. MacLellan believes the reason humans can’t regrow these vital cells is simple: When myocytes are in a more primitive state, they’re not as good at contracting, which is vital for proper heart function. Because humans are much larger than newts and salamanders, we need more heart contraction to maintain optimum blood pressure and circulation. “The way we evolved, in order to maintain blood pressure and flow, we had to give up the ability to regenerate the heart muscle,” Dr. MacLellan says. “The up-side is we got more efficient cardiac myocytes and better hearts. But it was a trade-off.”
By temporarily knocking down the proteins that block the cell-cycle mechanism, it may be possible to get adult cardiac myocytes to reenter the cell cycle and revert to a state where they can again proliferate, Dr. MacLellan says.
“This is a potential mechanism to regenerate heart muscle without having to harvest or expand stem cells,” Dr. MacLellan says. “Each person would be his or her own source for cells for regeneration.”