HOW TO HEAL A BROKEN HEART: Researchers are learning more about how to manufacture a patch that could help heart failure patients improve their tickers. Here, a working blood vessel in a cardiac patch after it spent a week in the stomach of a rat
TAL DVIR

Clinical trials are underway for stem cell injections to quicken healing of the cardiac muscle after a heart attack. Although promising results trickle in, other researchers are looking for a speedier way to renew a damaged area of the organ: patches of cardiac cells. One patch is getting a leg up from a temporary stay in stomach tissue, and another is using a biodegradable mesh to help the heart rebuild itself.

Patching a heart is certainly trickier than patching an old pair of blue jeans. A heart attack or other cardiac event often weakens and damages some of the muscle because of temporary oxygen deprivation. Thus, a patch must not only cover a damaged area of the heart, but it must also start helping to pump in its place.

Researchers in Israel set out to see if they could "employ the body as a bioreactor for the engineering of a cardiac patch," they wrote in their paper, published online today in the Proceedings of the National Academy of Sciences. They implanted patches of lab-grown heart cells onto rats' omentums—fatty tissue in the stomach that is rich in blood vessels and which has previously been used to foster regeneration of other organs. They left the patches on the omentums for a week before transferring them to the rats' intentionally damaged hearts.

The patch, initially grown on a mesh scaffold from the heart cells of neonatal rats and a mixture of compounds to aid development, had more blood vessels after spending a week on the rat's omentum compared with patches that were attached immediately onto the damaged hearts. Besides contributing to a thicker wall, the experimental patch integrated into the surrounding heart tissue better than the control patches, the authors report, especially in terms of its cells' synchronous firing with resident heart cells.

"Vasculature is very important," says Jordan Lancaster of the University of Arizona's Sarver Heart Center Tucson and the Southern Arizona Veterans Administration Health Care System who wasn't involved in the study but is also working on cardiac patch research. If a patch does not have enough blood flow to it, he notes, "cell survival is going to go down."

Lancaster would rather avoid connecting patches temporarily to another body part, an extra surgical step that is a cause of concern, especially for older patients. Instead, he and his team, led by Steven Goldman, also of the University of Arizona's Sarver Heart Center Tucson and the Southern Arizona Veterans Administration Health Care System, aim to implant patches directly on the heart, advances of which they described earlier this year in the journal Cell Transplantation. They have developed a biodegradable scaffold that gives heart muscle cells a three-dimensional structure on which to grow once it's inside the body. The scaffold is important because most stem cells simply injected into a damaged heart "don't survive," Goldman notes. "You need a supporting matrix."

Their patch is designed to disintegrate after about three weeks, leaving only newly grown tissue behind. Initial tests on lab rats have shown that the patch increases the heart's wall thickness and blood flow. They have also demonstrated that when a scaffold is seeded in the lab with 2.5 million or more neonatal rat heart muscle cells, the whole patch starts contractions on its own—results of which were presented last month at the American Heart Association's Cardiovascular Sciences Annual Conference in Las Vegas.

The scaffold (manufactured by San Francisco–based medical company Theregen, Inc.) is currently in phase I clinical trials to test for safety in people (it lacks any heart muscle cells). But a patch seeded with the heart muscle cells will have to wait for cardiac stem cells or induced pluripotent stem cells can supply them with a human-equivalent before testing.