Surgeons like to say that when someone suffers a heart attack, time is muscle. The heart depends on a continuous supply of oxygen from the coronary arteries; if these become blocked and that supply stops, the heart’s muscle cells start to die off within just a few minutes. In many cases, unless surgeons can relieve the blockage within the hour, more than 1 billion muscle cells are irreversibly lost.
Those who survive are often left with permanent heart failure – a group which includes approximately 450,000 people in the UK. Within the five years following an attack, 50% of them will no longer be alive. “Eventually their hearts become so weak that they can’t sustain sufficient blood flow and they just stop altogether,” says Sanjay Sinha, a cardiologist at Addenbrooke’s Hospital, Cambridge.
But even within the next five years, regenerative medicine may provide a radical new alternative: growing live, beating ‘heart patches’.
The challenge is that unlike some of our other organs, like the skin and liver, the heart has a very limited ability to self-heal. Heart muscle cells replicate at a rate of just 0.5% a year, not sufficient to repair any significant damage. Instead, the dead cells are replaced by thick layers of tough, rigid scar tissue, meaning that sections of the heart simply cease to function.
At the moment, the only medical option for patients with heart failure is a heart transplant. But a lack of donor organs means that just 200 of these operations can be performed in the UK each year. “I don’t think we could ever get the number of donors we need because you don’t get thousands of young people dying with healthy hearts,” says Sinha. “There’s only a very small pool of people who’ve died, in traffic accidents or through head injuries, where the heart is still strong and can be used for a transplant.”
Stem cell medicine may provide an alternative. In clinical trials, scientists have attempted to remuscularise damaged hearts by injecting individual stem cells – which can develop into many different types – from the patient’s blood or bone marrow directly into the heart.
While these approaches have successfully regenerated damaged blood vessels and thus improved blood flow to the heart, they have shown minimal benefit in terms of solving the major problem – growing back lost heart muscle. This is thought to be because 95% of the injected stem cells fail to attach to the heart and are immediately lost into the bloodstream.
But along with a team of stem cell biologists at the University of Cambridge’s Stem Cell Institute, Sinha is working on a slightly different idea: heart patches.
These tiny, beating pieces of heart muscle, each less than 2.5 sq centimetres (0.5 square inches) in area and half a centimetre thick, are made in small dishes in the lab. Grown over the course of a month, the patches are made by taking blood cells and reprogramming them into a particular form of stem cell which can be converted into any cell in the human body – in this case heart muscle cells, blood vessel cells, and the epicardium, the membrane around the heart which gives it its shape. These clusters of heart cells are then grown in a special scaffold which organises and aligns them into a formation resembling real heart tissue.