Scientists have grown a piece of heart muscle — and then watched it beat — by using stem cells from a mouse embryo, a big step toward one day repairing damage from heart attacks.
Think of Dr. Kenneth Chien as a heart mechanic. "We're making a heart part and (eventually) we're going to put the part in," is how he describes the work by his team of Harvard and Massachusetts General Hospital researchers.
Lots of work remains before trying that dramatic an experiment in people. But regenerating damaged heart muscle is a holy grail in cardiac care.
Doctors today have lots of treatments to prevent a heart attack. But once one strikes, there's no way to restore the heart muscle it kills. Gradually the weakened heart quits pumping properly, leading to deadly heart failure.
Hence the focus on embryonic stem cells, master cells that can give rise to any tissue in the body. Until now, scientists haven't known how to coax those cells into producing pure cardiac muscle.
Instead, researchers have tried injecting heart attack survivors with mixes of different kinds of stem cells, next-generation types like those found in bone marrow. The idea: Perhaps once those cells were inside a damaged heart, ones capable of growing cardiac muscle would receive a "get to work" signal and take root. There's been little success so far.
The new research, published in Friday's edition of the journal Science, promises a more targeted approach.
"It's not the home run," cautioned Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute, which is spending millions on research nationwide into cardiac regeneration. "But it's a major advance that's helping to move the field forward in a very significant way."
Embryonic stem cells give rise to more specialized organ-producing stem cells. The team from the Harvard Stem Cell Institute and Mass General recently discovered a master heart stem cell present in both human and mouse embryos.
But could they control it enough to make just the kind of heart cell they wanted to grow? They'd have to winnow out the daughter cell whose only job is to grow the muscle fibers of the ventricle, or pumping chamber.
Chien genetically engineered mice so that certain cells in the embryos' developing hearts would light either fluorescent red or green. As he watched the embryos grow, where the colors overlapped signaled developing heart muscle. Sure enough, when the team plucked out those cells, they were pure ventricle generators.
Next Harvard engineers pitched in with a special scaffolding. The team "seeded" the scaffolding with these ventricle stem cells, and a thin strip of mouse heart muscle grew right in the laboratory.
Not only that, it spontaneously beat, the team reported in Science and at a National Institutes of Health meeting this week on the state of cardiac regeneration.
"This looks like the kind of work a normal heart tissue strip would do," said Chien, director of Mass General's Cardiovascular Research Center. "We went from embryonic stem cells to an organ."
What next? This was not a fully developed piece of heart muscle but a thin strip. To be usable, it would have to be thicker, more three-dimensional, for more beating strength. It also needs a nourishing blood supply. So a next big challenge is pinpointing which daughter to those master heart stem cells will grow blood vessels.
The NIH's Nabel said the experiment also offers a possible new opportunity for cell therapy — that perhaps injecting the precise muscle-generating cell directly into a damaged heart would have a better chance of sticking and working.
The Harvard team wants both methods tried.
"We're not saying this is going to happen tomorrow," said Chien, who also is working on repeating the work with human cells. "I believe within five years," it might be ready to try with people.