Heart of the matter

An implant coated with stem cell-produced cells that encourage the body to heal itself could dramatically reduce the number of heart attacks and deaths in heart patients who have undergone surgery to clear blocked arteries.

The technology is being developed by a consortium involving stem cell company

, medical device maker

, the Centre for Stem Cell Biology (CSCB) and the Cardiovascular Research Unit (CVRU) at the

.

Led by Axordia, the team will spend two and a half years on pre-clinical trials to develop a new method of cardiovascular treatment that will encourage arteries to repair themselves.

The treatment involves implanting a new kind of stent — a tiny, metallic, mesh-like tube that keeps arteries propped open after artery-clearing procedures such as angioplasty.

The new type of stent will contain endovascular cells, created by stem cells, which have a remarkable ability to divide and replenish damaged tissue within the artery, so should promote rapid healing at the site of the implant. They will also reduce inflammation and act to prevent rejection of the implant.

Coronary artery disease causes at least 6.9 million deaths worldwide each year, and is the leading cause of premature death in the UK and western world.

In 2003, the UK spent 17 per cent of its healthcare budget on treating the disease. By reducing the need for patients to take expensive anti-clotting drugs for long periods, the regenerative stent could also save the NHS a large amount of money.

The development of a successful device could also lead to the production of other healing- promoting implants.

The use of coronary stents has been one of the most significant advances in the treatment of cardiovascular disease during the past 10 years. 'After an angioplasty has cleared the blocked tubes, a small scaffold is put in,' explained Tim Hall of Lombard Medical. 'Originally these were made of bare metal. However, placing them caused damage to the artery wall and more clotting, with the artery narrowing again after experiencing an inflammatory response.'

This condition, known as restenosis, occurred in up to 50 per cent of angioplasty cases, often requiring another operation to correct it. But the development of drug-eluting stents (DES) virtually eliminated the problem. These are metallic stents coated with cellular growth inhibiting drugs that prevent thickening of the vessel wall. The market created by them is worth up to $6bn (£4m).

However, there have recently been concerns about angioplasty patients developing late stent thrombosis, where the artery narrows at or near the stent site, allowing a clot to form that can cause a heart attack.

'Growth of the sector has tailed off,' said Hall. 'After surgery, patients take anti-clotting medication to prevent problems. If the medication is stopped, some people may develop thrombosis and even a heart attack. This is because the drugs stop inflammation but delay healing of the stent site as a side effect.'

Recent evidence suggests that patients who receive DES have higher rates of late stent thrombosis than those treated with bare metal stents. In over 50 per cent of cases, the condition results in either a heart attack or death.

It is thought that DES-related late stent thrombosis is due to the delayed healing of the vessel wall caused by the toxic effects of the drugs or, in some cases, the polymer used to deliver the drug. The longer the healing process takes, the more likely a patient is to have complications.

As a result, patients who have a DES procedure are now given anti-clotting drugs for up to 12 months, or longer, as a precaution against late stent thrombosis. These drugs are expensive and some patients cannot take them for long periods either because of cost or to complications from bleeding.

There is also the worry that if patients forget or are unable to take these drugs, even for a short time, they could be at risk, particularly if they undergo another surgical procedure, where the risk of sudden thrombosis is very high.

The involvement of Sheffield University's CSCB and CVRU should allow the consortium to move the technology quickly to clinical trials after the end of the project. The £1.8m programme is being part-funded with £400,000 from the DTI and £500,00 from the Medical Research Council.