Human stem cells fix heart damage in lab rats

Human embryonic stem cells have been used to regrow the heart muscles of rats that had survived lab-induced heart attacks, scientists from the University of Washington and a private biotechnology company reported Sunday.

Because the rebuilt heart muscle halted the progression of heart failure, the findings offer encouragement that treatments based on embryonic stem cells someday might be used to help people who suffer heart attacks, a leading cause of death in the U.S., said Chuck Murry, a UW researcher and an author of the study.

Unlike many tissues in the body, heart muscle cells don't regenerate. So when heart attacks cause heart cells to die, they are replaced by scar tissue, which doesn't beat. Often, that leads to outright heart failure and death.

Murry, director of the Center for Cardiovascular Biology at the UW's Institute for Stem Cell and Regenerative Medicine, has long struggled to use adult stem cells to re-create heart muscle. He and UW colleague Michael Laflamme, the lead researcher on this study, knew from other studies that human embryonic stem cells could become heart muscle cells in rats — an encouraging first step.

But in practice, only a tiny percentage of the stem cells were actually becoming heart-muscle cells. And most died quickly after being injected into rats' hearts.

After four years of research, Murry and his colleagues at Geron, a biotechnology company in Menlo Park, Calif., had a breakthrough: They found a process to coax as many as half the cells into becoming heart-muscle cells, and second, a way to keep the cells alive.

Not only did all the rats start getting new heart muscle, but they were protected from the progression of heart failure, Murry said.

"No one had ever grown human heart muscle back in an injured animal," Murry said. "We're pretty pleased."

The research is published in the September issue of Nature Biotechnology.

Like most research in this area, Murry's is incremental, building on his own previous findings and those of other researchers.

Funding for this study came partially from Geron, which hopes to develop medical products to help heart-attack survivors. Other funding came from the federal National Institutes of Health.

"There's an epidemic of heart failure coming on as baby boomers age," Murry said.

Stem cells are promising to researchers because they have the ability to turn into any kind of cell in the body. The challenge has been finding ways to control their transformations.

So for Murry and his colleagues, the problem was to get the cells to become heart-muscle cells instead of cells for livers, kidneys or something else. At first, they had little success, but then found certain proteins would trigger the right growth.

When they put the cells into damaged hearts, however, the cells died en masse.

"Almost everything we put in died," Murry said. "It's a very harsh environment. It's what killed the heart muscle cells to begin with, so maybe it's not surprising that it killed those cells."

The researchers tried one intervention after another. "We were trying to be very scientific, trying one approach at a time, but nothing worked," Murry said.

Finally, they hit on a "pro-survival cocktail" of chemicals and also applied heat to the cells to make them behave. "Lo and behold, in 100 percent of the animals we delivered the cells to, we saw grafts," Murry said.

About 10 percent of a damaged heart area was restored, enough to stop the progression of the heart failure.

That came as a surprise, Murry said. "The fact that if you can grow human heart muscle back, that prevents heart failure — we didn't know that."

The study, which ran for four weeks, didn't reveal what would have happened in the long run to the rats that got the stem cells.

To make the breakthrough, Murry and his colleagues used the so-called "presidential lines" of stem cells. Those cells are generated from a group of embryos that already had been destroyed before the Bush administration limited research on embryonic stem cells.

"We're pleased to be able to provide an example of something that can be done with embryonic cells that can't be done with adult stem cells," Murry said.

Murry hopes someday to work with newer lines that would be more suitable for human transplantation.

Carol M. Ostrom: 206-464-2249 or costrom@seattletimes.com