Bypassing surgery for new cardiac treatment

Coronary artery bypasses without surgery would deliver huge savings

Prof Noel Caplice, director of the Centre for Research in Vascular Biology at University College Cork,  displays his stent mesh. Photograph: Michael MacSweeney/Provision

Prof Noel Caplice, director of the Centre for Research in Vascular Biology at University College Cork, displays his stent mesh. Photograph: Michael MacSweeney/Provision

 

As Prof Noel Caplice describes it, a revolutionary new system that avoids putting patients through heart bypass operations was literally a “back-of- the-garage” effort.

A cardiologist in Cork, he came up with the treatment when working as a cardiologist at the Mayo Clinic seven years ago. During this time, Caplice and an engineer friend worked on prototype meshes and attaching these to stents.

The treatment introduces cells that encourage the body to make new blood vessels that grow past the blockage, actually reversing the disease in as little as three or four weeks.

The treatment may also offer hope for patients suffering from other cardiovascular disorders such as peripheral artery disease, a common risk in diabetes. And, because it uses the patient’s own cells, there is no question of rejection, says Caplice, director of University College Cork’s Centre for Research in Vascular Biology.

This would represent a major step forward in the treatment of coronary artery disease, he adds. Instead of open-heart surgery and stitching in arteries to bypass a blockage, it causes the body to grow its own bypass. He is leading the research, which also involves the Mayo Clinic in the US, and the team has published a paper describing the work in the current issue of the journal Biomaterials.

He came up with the idea when working as a cardiologist at the Mayo Clinic seven years ago, he says.

“One area we were interested in was patients who were inoperable, patients who were too ill to face open-heart surgery and who had no options. That represents about 20 to 25 per cent of all patients with coronary artery disease.”

He was a scientist physician while at the Mayo as he is now, doing research but also working with patients, and he ran his own laboratory. He originally thought of introducing stem cells to encourage blood vessel growth, “but when injected they go everywhere, you can’t direct them in the body.”

Caplice is also a consultant cardiologist at Cork University Hospital.

Mesh fibre carrier

He then came up with the idea of creating a “non-woven mesh fibre” carrier that could be connected to an ordinary stent, a device already used to treat narrowed or weak arteries.

The idea was to load the mesh with smooth muscle cells, the kind of cells found in the heart, then use the mesh to insert them close to the site of the arterial blockage.

It took him five years to develop the idea, during which time he relied on outside expertise. It was literally a “back-of- the-garage” effort when he got an engineer working in his garage to develop prototype meshes and attaching these to stents.

Getting the muscle cells to attach and grow to the mesh was a particular challenge. He tried many different coatings until he came up with one that allowed the cells to thrive and multiply. Cells can be taken from the patient and large numbers grown up within a week, but he only needs a day to fill up the mesh with cells.

“We can load up about two million cells per square centimetre of mesh,” he says.

Once he had a carrier for the cells, he could deposit the device in the artery near the blockage and then let the cells and the body take over, he says. “The cells don’t make the new blood supply, the body does it.”

Self-supporting

The cells encounter a low oxygen environment, given the blockage, and they begin to send out a signal for the body to improve oxygen supply. The heart-like cells begin releasing factors that stimulate the growth of the vasa vasorum, the network of small blood vessels that supply the large blood vessels and these begin branching across the blockage.

“It is huge. You have only one stimulus but once the body is recruited it becomes self- supporting,” Caplice adds.

“These cells stay around for weeks and stimulate the system. The key is we have a captive population [of cells] that keeps on pushing the signal for three or four weeks and the body does the rest.”

The research team tested the device on pigs which have similar-sized blood vessels.

“You can block an artery and within four weeks, the micro bypasses form,” he says. “We also do stress tests but the treated pigs perform like a healthy pig.”

He believes, however, that the medical community will “need a lot of convincing”, given this unorthodox use of a conventional stent as a delivery system. It will also require a “major commitment” from any company that wants to develop this device and bring it to market.

He received funding for his research from the National Institutes of Health Heart, Lung and Blood Institute in the US and subsequently from Science Foundation Ireland here, but a company might have to spend €200 million-€300 million before it could be used as a treatment.

However, being able to provide a coronary artery bypass without surgery would deliver huge savings to health services, given there are about three million open-heart bypasses and peripheral artery bypasses performed a year worldwide.

Caplice also thinks of the large numbers of patients who cannot hope for a surgical response to their condition.

“They are stuck at home and can’t get out,” he says. “These are not patients who are dying, they have really chronic disease and they have time to wait for a treatment.”

Unfortunately it will involve a wait. He believes that at best it would take at least five years to begin early human trials. Success, however, would transform the lives of those with the disease.