Researchers seeking new treatments for heart disease

Researchers Restart Rat Heart

Researchers seeking new treatments for heart disease managed to grow a rat heart in the lab and start it beating.

"While it still sounds like science fiction, we've hopefully opened a new door in the notion that we can build these tissues and one day provide options for patients with end-stage disease," said Dr. Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota. "We're not there yet, but at least now we have another tool in our tool belt."

Taylor led the team whose research appeared in Sunday's online edition of the journal Nature Medicine.

Scientists have worked for years for ways to grow body parts. Many efforts have focused on heart valves as an alternative to the plastic or animal valves that wear out after being implanted in humans.

An estimated 5 million people live with heart failure and about 550,000 new cases are diagnosed each year in the United States. Approximately 50,000 die annually waiting for a heart donor.

Taylor said in a telephone interview that her team began by trying to determine if it were possible to transplant rat heart cells. They took the hearts from eight newborn rats and removed all the cells. Left behind was a gelatin-like matrix shaped like a heart and containing conduits where the blood vessels had been. Scientists then injected cells back into this scaffold -- muscle cells and endothelial cells, which line blood vessels.

The muscle cells covered the matrix walls and lined up together, while the endothelial cells found their way inside to coat the blood vessels, she said. Then the hearts were stimulated electrically.

"By two days we saw tiny, microscopic contractions, and by seven to eight days there were contractions large enough to see with the naked eye," she said. The tiny hearts could pump liquid at about one-fourth the rate of a normal fetal rat's heart.

"Obviously we have a long way to go," Taylor said. But the long-term hope, she said, is that a similar process could work with either human hearts from cadavers or pig hearts, with their cells stripped off and replaced by cells from the person needing a heart transplant to avoid rejection.

The next step is to take a pig heart, strip away the cells and repopulate it with cells from a pig to see if it will work in the larger heart.

Dr. John Mayer Jr., a heart specialist and researcher at Children's Hospital in Boston, said the report was an "important paper that advances the ball down the road." But, he added, "It's pretty long road."

Mayer, who was not part of Taylor's research team, noted that this was done in a small animal and it remains to be seen whether the same can be done in larger ones. He also wondered whether blood would flow freely, without clotting, through the reconstructed blood vessels.

"I think this is an important contribution, with more work to be done," Mayer said in a telephone interview.

In her research paper, Taylor also reports that the researchers are working on reseeding cells into other organs, including lungs, liver and kidneys.

The research was funded by the University of Minnesota and the Medtronic Foundation, the charitable arm of a medical company that makes heart devices such as stents and defibrillators.

New treatment for heart attacks
A team led by scientists at The Scripps Research Institute has developed a potential new treatment for heart attacks. The therapy inhibits fluid leakage from cardiac blood vessels following a heart attack and thereby significantly prevents long-term heart damage and improves survival.

"Immediately following a heart attack, blood vessels near the site of injury become leaky, causing fluid accumulation in the healthy area of the heart surrounding the injured site," says Immunology Professor David A. Cheresh, Ph.D., who led the research with postdoctoral fellow Sara Weis, Ph.D at The Scripps Research Institute. This permeability response is devastating to normal heart tissue.

"Until now," continues Cheresh, "nobody has realized the extent to which this leak response damages heart tissue and causes long-term tissue injury. We discovered a way to block this process and thus save heart tissue from irreversible damage."

Using laboratory models that are designed to mimic the pathology of heart attacks in humans, Cheresh, Weis, and their colleagues found that a single dose of a compound designed to block this fluid leakage (which is called edema) can, even if given as late as six hours after the event, drastically reduce tissue injury and increase long-term survival following a heart attack.

A biopharmaceutical company, TargeGen Inc. in San Diego, is finalizing preclinical studies to translate these initial research findings into practical human therapies. Using extensive preclinical models that mirror human heart attacks, TargeGen scientists report that 40 to 60 percent reductions in infarct (tissue injury) size with a small molecule drug that inhibits vascular leak and edema. Based on the encouraging preclinical efficacy and safety studies, TargeGen plans to initiate a combined Phase I/II human clinical trial in the second half of 2004 for patients undergoing an acute heart attack.

In addition to Cheresh and Weis, the team included scientists from St. Elizabeth's Medical Center at Tufts University School of Medicine in Boston, Massachusetts; the Department of Radiology at Beth Israel Deaconess Medical Center in Boston; and the private company TargeGen, Inc. of San Diego, California.