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Injected 'Hydrogel' May Help Repair Failing Hearts
Date:2/20/2013

By Carina Storrs
HealthDay Reporter

WEDNESDAY, Feb. 20 (HealthDay News) -- An injected "hydrogel" could someday become a nonsurgical means of repairing damaged cardiac tissue in patients with heart failure, a new study suggests.

The material used is based on pig heart tissue. It has proven effective when tested in pigs with failing hearts, and may be a step closer to being an option for patients.

Researchers at the University of California, San Diego, demonstrated that they could inject the hydrogel into the hearts of pigs two weeks after a heart attack and prevent the loss of cardiac muscle and other changes that can eventually lead to heart failure.

"After a heart attack, not only do cells die but the natural scaffold where the cells sit gets degraded and cleared," explained lead researcher Karen Christman, an assistant professor of bioengineering at UCSD.

"We think the hydrogel provides a temporary physical scaffold that allows the body's own surviving heart cells to repopulate that area, and allows new blood vessels and stem cells to come in, and the net result is we get more cardiac muscle in that region," she said.

So far, the research suggests that the pig-derived hydrogel could be well tolerated by other species. The researchers also injected the material into rat hearts and did not see the type of inflammation that indicates the body is rejecting the material.

This immune tolerance is probably due to the fact that the researchers wash away all the cells from the pig hearts, so that all that is left in the hydrogel are proteins and sugars, Christman explained. Once the proteins are injected into the heart, they self-assemble into a "tangled mess of fibers" that becomes the scaffold, she said.

If the hydrogel makes it to market, it would not be the first pig-derived clinical product. According to Christman, more than one million people have been implanted with material made from pig small intestine to treat injured arteries, repair bladder tissue, tendons and ligaments.

She and her colleagues are planning to begin testing the pig heart hydrogel in people who have had a heart attack, starting in the second half of 2013.

For the treatment, doctors would deliver the hydrogel via a catheter running from an artery in the groin up to the damaged part of the heart, similar to how the material was administered in pigs, Christman said.

Another type of hydrogel that is made from seaweed was shown to have benefit in pigs and is currently being tested in a clinical trial for its safety and effectiveness in people who are at risk for heart failure.

More than 900,000 Americans have a heart attack every year, according to the U.S. Centers for Disease Control and Prevention. Heart attacks can increase the risk of heart failure, which occurs when the heart can't pump enough blood, and is marked by shortness of breath, coughing and fatigue. Approximately 5.7 million people in the United States have heart failure.

"When you have a heart attack, those heart cells die and turn into scar tissue, and over time the heart enlarges and becomes less efficient," which can lead to heart failure, said Dr. Jay Traverse, an associate professor of medicine at University of Minnesota Minneapolis Heart Institute.

Medications, such as ACE inhibitors and beta blockers, or tiny mesh stents to open up the artery can help prevent heart failure in a lot of people, he said. "But still a lot of people go on to develop heart failure, so the drugs are not enough," he explained.

"The two main areas that look promising are using stem cells and the use of these biomaterials that [Christman's] paper addresses," Traverse said.

A number of researchers, including Traverse, are studying the effects of injecting stem cells via a catheter into patients' hearts after a heart attack in the hope of spurring regrowth of cardiac muscle and preventing heart failure. The stem cells come from the heart or bone marrow of the patient or a donor.

The results have been mixed, with some studies reporting improvements in measures of heart pumping efficiency whereas others have not found differences in heart function.

One issue with stem cell treatment is that only about 10 percent of the stem cells survive for more than about a day after injection, probably because they do not have a surface to adhere to, Traverse said.

In contrast, Christman's study showed that, in rats, the hydrogel scaffold stuck around for a couple of weeks before it dissolved. By that time, the scaffold has probably recruited enough stem cells and salvaged enough heart muscle cells to have a lasting benefit, Traverse said.

He and his colleagues are currently testing the use of stem cells in animals in combination with the pig intestine-derived material, which is U.S. Food and Drug Administration-approved. "We hope that we could potentially have an additive effect," Traverse said.

The current study by Christman and her colleagues administered the hydrogel to six pigs and gave an injection of salt solution or no injection to four "control" animals.

The researchers tested the heart function of the pigs by echocardiogram, or "echo," which uses ultrasound to take pictures of the heart.

Three months after the injections, the pigs that received the hydrogel showed improvements in measures of how well their hearts pumped blood, and reductions in measures of heart enlargement that can indicate heart failure. In contrast, most of the control animals had deteriorated heart function and signs of heart enlargement.

The researchers looked at heart tissue taken from the animals and found that the hydrogel-treated animals had thicker heart muscle in the region of the heart attack than the control animals. There were no differences in heart rhythm or in tissues from other organs after the injections in either the treated or control animals.

Although the true test will be how effective and safe the hydrogel is in people, the pig heart anatomy is very similar to humans, Christman noted.

"I imagine in 15 years from now when patients come in after a heart attack [and show signs of heart failure based on echo or MRI tests], they are going to get stem cells or biomaterial product or both to help prevent the development of heart failure," Traverse said.

The study was published in the Feb. 20 issue of Science Translational Medicine.

The research was funded in part by Ventrix Inc., a San Diego-based company that Christman cofounded and that has licensed the hydrogel and its delivery methods.

More information

There's more on heart failure at the American Heart Association.

SOURCES: Karen L. Christman, Ph.D., assistant professor, bioengineering, University of California, San Diego; Jay H. Traverse, M.D., associate professor, medicine, University of Minnesota, senior cardiology associate, Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis; Feb. 20, 2013, Science Translational Medicine


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