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Living heart valves grown in laboratories

A heart valve made of a patient’s cells could be implanted into their body and naturally grow with them. Image courtesy of LifeValve

Cells could be taken from babies born with severe heart defects and used to grow living replacement valves in a laboratory, if technology under development proves successful in real-life trials.

Up to 1 % of babies are born with severe heart defects, and with current technology that means multiple rounds of open-heart surgery as the child grows.

The Issue

The most common treatment for heart defects which are present from birth is a combination of surgery and catheterisation - where a long thin tube is threaded through the blood vessels to the heart, allowing doctors to do diagnostic tests.

Surgery is often first performed in very young babies, as early treatment can be the most effective way of repairing the heart.

As a result of these proceures, most children born with heart defects go on to live normal healthy lives.

However, techniques under development by a trans-European research collaboration known as LifeValve would require just one minimally invasive heart operation as the tissue would then grow naturally with the child.

‘We've been able to show that the technologies work, and have secured enough funding to finish the project and fulfil the regulator's requirements for starting a large-scale clinical trial,’ said Professor Simon Hoerstrup, head of the Swiss Center of Regenerative Medicine at the University of Zürich.

The cells are placed onto a 3D scaffold and left to multiply. Eventually the scaffold disintegrates, leaving just the living tissue heart valve.

The EU-funded project is part of a revolutionary field of medicine known as tissue engineering where doctors hope to use a patient’s own cells to grow replacement body parts in the laboratory.

One of the major goals of tissue engineering is to grow a complete, fully functioning organ, and in 2011 surgeons in Sweden took a step in this direction, successfully carrying out the world’s first synthetic organ transplant. They covered an artificial replacement windpipe with live cells grown from the patient’s own body and implanted it in a 36-year-old Eritrean cancer patient.

3D printing

One of the key techniques being used in tissue engineering is to use 3D printing to build scaffolds so that live cells can be grown in the desired shape.

Dr Declan Devine is at the cutting edge of scaffold technology. He travelled from Ireland to Harvard University in the US as part of the EU’s Marie Skłodowska-Curie action to develop scaffolds that incorporate proteins to encourage cells to multiply, making the scaffold cheaper and more effective, under a research project known as NANOFACT.

‘We've been able to show that the technologies work.’

Professor Simon Hoerstrup, Director, Swiss Centre of Regenerative Medicine, University of Zürich

Normal scaffolds need the patient to undergo significant surgery to get enough cells, he said. ‘In that sense our scaffolding using growth factors and naturally occurring products in synthetic matrixes enables us to get away from that.’

Now his Marie Skłodowska-Curie grant is over and he’s looking for funding to start testing his technology in people. If he is successful, he believes he could start trials in people in two years.

However, it will still be years until tissue engineering is on offer to patients.

That’s why the TECAS training project, funded by the EU, is bringing researchers from disciplines such as medicine, biology and engineering together with representatives from industry.

‘Getting them together around one table from the beginning … is significantly accelerating the process and shortening the time it takes for a medical invention to move from the bench to the bedside,’ said Dr Sotirios Korossis from the coordinating institution, the Hannover Medical School in Germany.

‘Normally, it would take 10 to 20 years to reach the market. With TECAS we are looking at five to seven years.’ 

  • The four valves in the human heart.

    In 1923, US surgeon Dr Elliot C. Cutler repaired the so-called mitral valve in a 12-year-old girl’s heart, the first known successful heart valve surgery. The mitral valve is one of four valves in the human heart and, along with the aortic valve, is the most likely to be damaged. The other two valves – pulmonary and tricuspid – are under less pressure and do not often wear out.
  • A modern heart-lung machine. Credit: Creative Commons/Jörg Schulze

    In a breakthrough for heart surgery, surgeons in Philadelphia, US, carried out the first successful heart operation using a heart-lung bypass machine, which takes over the tasks of breathing and pumping blood while the patient is having surgery. It means that the heart can be stopped, enabling easier manipulation by the surgeon and its introduction paved the way for rapid advancements in open heart surgery.
  • Surgeons implementing a mechanical heart valve. Credit: Shutterstock/pirke

    In 1960 the first aortic valve was replaced by a mechanical valve, followed by a mitral valve replacement in 1961. Mechanical valves are still used today and are likely to have a long lifespan; the disadvantage is that the patient needs to take anti-clotting medication for the rest of their lives to prevent complications.
  • Pig valves can be used to replace human heart valves. Credit: OpenWetWare

    During the 1960s, valves and tissues taken from pigs, cows and human donors began to be used to replace human heart valves, and are still used today. Animal tissue needs to be treated so it is not rejected and generally it takes around four weeks for a pig heart valve to be prepared for transplant into a human. Bovine valves are not taken directly from a cow, but are made from the cow’s heart tissue. All these bio-based valves have the advantage of not requiring the patient to take anti-clotting medicine, but generally do not last as long as mechanical valves.
  • Doctors can use endoscopes in heart valve replacement surgeries. Credit: Creative Commons/ Linda Bartlett

    Developments such as spring-loaded and balloon-expandable valves means that surgeons are able to insert them through tubes known as catheters and expand them when they reach their destination. While this does not remove the damaged valve, it is a less-risky option for people who may not survive an operation. In 2014, French surgeons carried out the first complete heart valve replacement using an endoscope - a long, flexible tube inserted through two small incisions - indicating that full valve replacement surgery could become minimally invasive in the future.

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