January 21, 2008

Magnets Improve Coronary Stents

PHILADELPHIA -- When cardiologists prop open blocked arteries with the lifesaving metal cylinders known as stents, inevitably there is some damage to the cells that line the blood vessel walls _ damage that may not heal properly on its own.

A team of Philadelphia researchers now thinks it can address the problem by borrowing a trusty concept from Physics 101: magnets.

The scientists implanted stents in the carotid arteries of rats, then placed the animals between two large electromagnets, temporarily magnetizing the stents. The rats were then injected with healthy repair cells that had been loaded with tiny magnetic particles, which were simply drawn through the bloodstream to the right location.

The procedure, reported this month online and in the print issue of Proceedings of the National Academy of Sciences, is just one way researchers are exploring the use of magnets as medical tour guides through the byways of the human body.

The authors of the paper, from Children's Hospital of Philadelphia and Drexel and Duke Universities, also envision using magnets to deliver drugs and even designer genes _ and not just to the insides of arteries. Stents used in the bile duct, urinary tract, esophagus and lungs also could be targeted _ as could other kinds of metal implants that are used in orthopedic procedures.

Biomedical engineer Robert S. Langer, a Massachusetts Institute of Technology professor who was not involved with the paper, praised the new research for its "cleverness."

"It seems to me that could be universally applicable," Langer said.

In blood vessels, the goal of the magnet-based therapy is to help prevent stented arteries from becoming reobstructed, whether by blood clots or abnormal cell growth. Further study is needed, and the procedure is a few years from being tried in humans.

There's a big market for it. Bare-metal stents were approved for use in 1994, followed by the advent of the drug-coated variety in 2003. They've become so popular for use in heart patients _ more than 600,000 were implanted in 2004 nationwide _ that coronary bypass operations have declined as a result.

But both kinds of stents can have unwanted consequences, such as damage to the clot-resistant endothelial cells that line arteries, said cardiologist Robert J. Levy, senior author of the new paper.

When bare-metal stents are implanted, sometimes abnormal smooth-muscle cells will grow before the endothelial cells can heal, reobstructing the artery. Drug-coated stents help prevent this abnormal growth, but they also inhibit the regrowth of healthy endothelial cells, so blood clots are a concern.

Solution: Deliver healthy endothelial cells to the proper location.

That's where the magnets come in, said Levy, who directs the cardiology research laboratories at Children's Hospital.

First, the team loaded the endothelial cells with magnetic nanoparticles _ tiny spheres of a biodegradable polymer that had been impregnated with iron oxide. These cells were then injected into five stented rats that sat between the magnets.

The cells had been engineered to have a luminescent "reporter gene," so once they stuck to the stents, they could readily be seen with the proper imaging equipment, Levy said. Sure enough, the glowing particles were visible in the very diamond-shaped pattern of the mesh stents to which they adhered.

Drexel's Boris Polyak, the co-lead author of the paper, said further study was needed to see if such cells would grow permanently into the surrounding tissue.

"We expect them to adhere, to proliferate, and to grow," Polyak said.

When the stents were examined soon after the injections, the cells already had begun to attach to the artery wall, Levy said. (The researchers used cells from a cow because they were readily available, but they plan to follow up with a rat's own endothelial cells.)

The polymer used to make the particles is of the same kind already used for biodegradable sutures, and it is easily broken down by the body. The iron oxide was at low enough levels that it was cleared by the rats' cells with no ill effects.

But Levy said in the future, his team hopes to make nanoparticles with even lower levels of iron oxide.

That would be possible if physicians made use of the much stronger magnetic field in a device that is already widely found in hospitals: the MRI machine.

The magnetic field in an MRI is about 10 times stronger than what was used with the rats; as a result, physicians could use magnetic particles with much less iron oxide, he said.

MIT's Langer said he wasn't sure that an MRI machine could be used for this purpose without modification. So testing the machines is among the next projects in Levy's lab.