By David Cox
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.
“We believe that these patches will stand a much greater chance of being naturally assimilated into a patient’s heart, as we’re creating fully functional tissue which already beats and contracts through combining all these different cell types which communicate with each other,” Sinha says.
“We know the epicardium cells are particularly important in co-ordinating proper development of heart muscle because research has shown that in developing embryos, there’s a lot of crosstalk which occurs between the epicardium and the developing heart.”
Sinha is currently preparing to trial the patches, first in mice and then pigs. If all goes to plan, in five years he may be ready to conduct a first human trial.
He’s not alone. In the US, a collaborative team of scientists from Stanford University, Duke University and the University of Wisconsin are also trying to build heart patches.
Like Sinha, they envisage a future procedure where a combination of ultrasound and MRI scans are used to locate the scarred structures in the heart. Based on the shape of the scarring, they’d then 3D print a custom heart patch of any shape or dimension. Surgeons would open up the chest cavity and stitch the patch directly to the heart in a way that links it up with the existing veins and arteries.
“For patients with particularly severe heart failure, multiple patches will be required in multiple places as the whole heart dilates to try to adapt to the damage,” says University of Wisconsin regenerative biology professor Tim Kamp, who is part of the collaboration. “It changes shape from being like a rugby ball to a big balloon or basketball.”
One of the main challenges with this approach is how to electrically integrate the new patch with the heart to ensure that both beat in synchrony. Any defective electrical connections could stimulate an abnormal heart rhythm.
“We can put the patch on the heart with our surgical tools but we can’t force them to shake hands,” Kamp says. “But we hope they will. We anticipate that the electrical signals which pass through the heart muscle like a wave and tell it to contract will drive the new patch to contract at the same rate.”
Here are the cells from the Stanford University heart patch up close:
If these challenges can be overcome, Sinha believes they could save not only lives, but dollars.
In the UK, heart transplant procedures cost around £500,000 ($690,000) including inpatient care. But for the thousands of heart failure patients who are not able to get a transplant, the cost implications of continuous medical care and repeated hospital admissions can be even bigger. By contrast, current estimates place the potential cost of a heart patch treatment at around £70,000 ($96,000).
In addition, because the patches are made using their own blood, patients undergoing the procedure would not have to undergo some of the complications associated with heart transplants – like high doses of immunosuppressant drugs. “An injured heart is a highly inflamed, hostile environment which can be difficult for new tissue to survive in,” Kamp says. “The advantage of these heart patches is that they’re personalised to the patient, so the heart is unlikely to reject them.”
The technology could change the lives of millions around the world, the researchers say.
“Heart failure can pretty much incapacitate people,” says Sinha. “You’re constantly exhausted, you can’t even climb a flight of stairs. But for the first time, we think we’re actually able to recreate real living heart tissue, which is identical to that of the patient, where the cells are talking to each other in mysterious and wonderful ways and working together as they do in the body.
“If we can fine-tune it in the next few years, and make sure it’s completely safe, then it could help these people live a normal life again.”
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