Scientists try to heal heart with stem cells

Hopkins researchers hope to fix organ after an attack

Cells generate new cardiac tissue

December 13, 2004|By Jonathan Bor | Jonathan Bor,SUN STAFF

While scientists, politicians and theologians were debating the ethics of using embryonic stem cells to treat disease last year, researchers in New York made a startling discovery.

What they found was a reservoir of stem cells in the heart -- cells programmed to generate new cardiac tissue. The discovery crumbled a centuries-old medical dogma: that we are born with all the heart cells we'll ever have -- and that the heart can't be repaired once it is damaged.

Now, scientists across the United States and Europe are trying to harness those "adult" cells to regenerate failing hearts and reduce the need for extreme therapies such as transplants.

"I wouldn't want to advertise this as a panacea, but ... it opens up a completely new avenue that we didn't know about a year ago," said Dr. Eduardo Marban, chief of cardiology at the Johns Hopkins School of Medicine and a leader in efforts to harness the cells. "It really has the potential to revolutionize the field."

Though many questions remain, doctors hope to see the day when they can fix damaged heart muscle by seeding it with stem cells grown in a lab. While Marban and like-minded researchers pin their hopes on cardiac stem cells, others say a better source might be a type of stem cell found in bone marrow.

Progress is occurring rapidly. Marban, for instance, has watched cardiac stem cells morph into tiny collections of cells -- called cardiospheres -- that beat like miniature hearts. Given to mice soon after heart attacks, the stem cells reduced scarring and helped the muscle pump more vigorously.

Hopkins cardiologist Dr. Joshua Hare has shown that stem cells from the bone marrow of pigs helped other pigs recover from heart attacks. Hare, who joined Marban in presenting findings at last month's meeting of the American Heart Association, hopes to begin safety trials in humans next year.

Ethics and discovery

Whether the cells are derived from the heart or bone marrow, such therapies are likely to sidestep the ethical dispute over research into embryonic stem cells, which are culled from fertilized eggs that opponents argue are potential humans.

"The idea of purposely creating new products of conception so we can destroy them and harvest stem cells is never going to be something society can universally accept," said Marban, who said he supports research into embryonic cell therapies.

Dr. John Gearhart, a Hopkins developmental biologist and stem cell pioneer, said he welcomes the developments even as he continues his research into embryonic cells.

"This is exciting," said Gearhart. "Here is an organ we didn't think had any regenerative capacity, but they harbor stem cells. Now we know of several sources where you can perhaps get [heart muscle cells] to use in grafts."

The notion that the heart can't be repaired was based on the fact that patients who suffer heart attacks are left with patches of dead tissue that scar over but never heal. Drugs, exercise and diet changes can help patients regain normal activities, but they don't get their old hearts back.

So, when scientists at New York Medical College in Valhalla, and later at Baylor College of Medicine in Houston, found cardiac stem cells in rodents, it raised a question: What do the cells do?

"One would have to say at the moment that there is no direct proof for what any of these [cells] do," said Dr. Michael Schneider, a professor of medicine at Baylor who published his findings in September.

Clearly, they are incapable of major repair work or the heart would regenerate naturally after an attack. But they might perform a type of low-level maintenance during a person's life, a process Hare likens to oil changes and tune-ups on a car.

With the riddle unsolved, scientists wondered whether the stem cells could be enticed to do more than nature intended.

Marban's hope is to obtain tiny specimens of heart tissue from patients, coax the tissue to generate millions more stem cells, and then return the cells to patch damaged sections of the heart. Though he might be a year away from the first stage of human trials, Marban said, he is encouraged by what he sees.

Working with a colleague from the University of Rome, he obtained tissue samples from transplant patients whose hearts had to be tested anyway for signs of rejection. The samples were withdrawn with a catheter, a tube that doctors snake through an opening in the groin to one of the heart's pumping chambers.

After chopping the specimens into grains, scientists placed them in tissue cultures and watched as they spawned halos of stem cells that developed into beating cardiospheres.

"These little spheres began to look like little hearts in a dish," Marban said.

Injected into mice that had suffered lab-induced heart attacks, the cells appeared to regenerate tissue and restore pumping capacity.

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