Broken hearts found to mend themselves

Stem cells apparently try to mend hearts damaged by heart attacks or high blood pressure. But they do not refresh hearts run down by aging.

Evidence for this heartening and disheartening news comes from experiments with mice done at Harvard Medical School (HMS) and Brigham and Women’s Hospital in Boston.

“Our results show that stem cells may be activated to form new heart muscle cells after major stresses like heart attacks and high blood pressure,” says Richard Lee, an associate professor of medicine at HMS. “However, we also found that during normal life these cells are not being actively replaced at a significant rate. We speculate that there is some ongoing heart regeneration as we age, but this occurs at a very low level. But when a major injury occurs, stem cells become activated — in an as-yet-unknown way — to create new heart cells.”

Lee and his colleagues describe their experiments in the August issue of the medical journal Nature Medicine

Such experiments cannot be done on humans so researchers used the next best thing, mice, which boast human like hearts but live out their lives in about two years.

Although the world is enthusiastic about growing new hearts, no one knows how to go about it. One of the questions to answer first is, “How much cell regeneration is actually going on and how is it being done?” To probe deeper, Lee’s team introduced custom-tailored genes that allow heart cells to be marked with a fluorescent green dye. “It’s a way to tag heart cells at a particular time in life, a way to have each one punch a time clock,” Lee says.

The researchers put these magic markers on the cells of young mice. After one year, about half a lifetime for a mouse, they counted the marked cells. If stem cells had replenished the rodents’ hearts, the new cells would have no glowing green markers. Thus, there would be fewer tagged cells in older mice.

As it turned out, however, the number of dyed cells did not change. This is novel evidence that stem cells don’t constantly replace heart cells at a very refreshing rate.

Regenerating human hearts

The team also conducted the same experiment with mice that suffered induced heart attacks or surgical overloads that simulated high blood pressure. The results indicated that more than 7 percent of the cells so stressed had been replaced, presumably by stem cells that turned into new heart cells.

“These data suggest some regenerative response is activated by injury,” Lee explains. “But it’s not nearly enough. It’s not enough to repair the heart in the same way that an injured leg muscle repairs itself. So we need to learn what is holding it back, and how we can turn off that brake in humans and encourage more regeneration to occur.”

One big question to answer is whether or not it truly is stem cells that are doing all the work. There may be immature heart cells present that can be triggered into maturity to take over some of the workload. Such so-called “precursor cells” are already committed to becoming part of the heart. Stem cells, on the other hand, are self-renewing and also can turn into other types of cells.

Another question concerns what happens in older mice. Is it possible that heart attacks and disease can’t generate new cells when hearts are older? “We are trying to answer that question now,” Lee notes. “It’s so important because most heart injuries occur later in life.

“Our experiments just provide one piece of the puzzle,” he continues. “So most of us don’t feel that we’re going to be regenerating human hearts in the next year or two. But if we understand more about what’s going on at the most basic level, we’ll make more logical decisions about what strategies may work in people.”

This kind of effort is also going on at other laboratories. Many groups who have found stem cells or precursor cells in the human heart are thinking of ways to introduce more of them into that life-sustaining pump to see if they will grow and replace damaged tissue.

“We need to understand the fundamentals about what these cells are doing, and when, before we’ll be able to grow new heart muscles in humans,” Lee concludes. “To do this will require the whole orchestra of the scientific community playing together.”