Cryogenically frozen hearts could one day be used in transplants

Scientists have succeeded in cryogenically freezing and rewarming sections of heart tissue for the first time, in an advance that could pave the way for organs to be stored for months or years (The Guardian, 2017).

If the technique scales up to work for entire organs, and scientists predict it will, it could save the lives of thousands of people who die each year waiting for transplants.

The work is being hailed as a major development in the field of cryopreservation as it marks the first time that scientists have been able to rapidly rewarm large tissue samples without them shattering, cracking or turning to a pulp. The team at Tissue Testing Technologies in Charleston, South Carolina overcame this challenge by infusing the tissue with magnetic nanoparticles, which could be excited in a magnetic field, generating a rapid and uniform burst of heat.

Kelvin Brockbank, chief executive officer of Tissue Testing Technologies and a co-author of the study, said “It is a huge landmark for me. We can actually see the road ahead for…clinical use and getting tissues and organs banked and into patients.”

Currently, donor organs such as hearts, livers and kidneys must be transplanted within hours because the cells begin to die as soon as the organs are cut off from a blood supply. As a result, 60% of the hearts and lungs donated for transplantation are discarded each year, because these tissues cannot be kept on ice for longer than four hours. Recent estimates suggest that if only half of unused organs were successfully transplanted, transplant waiting lists could be eliminated within two to three years. Mehmet Toner, a professor of bioengineering who is working on cryopreservation at Harvard Medical School, said: “It’s a major breakthrough. It’s going to catalyse a lot of people to try this in their laboratories. I’m impressed.”

Cryopreservation has been around for decades, but while it works well for red blood cells, sperm and eggs, scientists have come up against a barrier for samples with a volume larger than around one millilitre. Previously, larger samples have been cooled successfully using a technique known as vitrification, in which the tissue is infused with a mixture of antifreeze-like chemicals and an organ preservation solution. When cooled to below -90oC, the fluid becomes a glass-like solid and prevents damaging ice crystals from forming.

The real problem has been the thawing process. Unless the rewarming occurs rapidly and uniformly, cracks will appear in the tissue and tiny ice crystals suddenly expand, destroying cellular structures. Mehmet Toner said “We can freeze tissue and it looks good, but then we warm it and there are major issues.”

The latest work scales up cryopreservation from 1ml to about 50ml, and the scientists said they believe the same strategy is likely to work for larger skin transplants, sections of ovarian tissue and entire organs.

John Bischof, professor of mechanical engineering at the University of Minnesota and the senior author of the study, said “We have extremely promising results and we believe that we’re going to be able to do it but we have not yet done it.”

Kelvin Brockbank and colleagues previously attempted and failed to use microwave warming to generate an even thawing. He said “It failed dreadfully due to the development of hotspots in the tissue.”

In the latest paper, published in Science Translational Medicine, the team describe the new nano-warming technique. Pig heart valves and blood vessels were infused with a cryoprotectant solution mixed with iron oxide nanoparticles, coated in silicon to make them biologically inert, and the samples were cooled in liquid nitrogen to -160oC. For thawing, the sample was placed inside an electromagnetic coil, designed to generate an alternating magnetic field. As the magnetic field is flipped back and forth, the particles jiggle around inside the sample and rapidly and uniformly warm tissue at rates of 100 to 200oC per minute, ten to a hundred times faster than previous methods.

In tests of their mechanical and biological properties, the tissues did not show any signs of harm, unlike control samples rewarmed slowly over ice. The researchers were also able to successfully wash away the iron oxide nanoparticles from the sample following the warming, although said that further safety testing would be required before the technique could be used in patients.

The team are now testing the technique on rabbit kidneys and human allografts. Kelvin Brockbank said “That will be our first trial with human tissues. If that is successful, we would then progressively move to structures such as the human face for banking and for hands for banking as well as digits.” However, he said it was difficult to put a timeline on when the developments might have a clinical impact, as this depended on regulatory approval as well as overcoming significant scientific challenges.

The researchers acknowledged their work may attract interest from the cryonics industry, which promises to freeze the bodies or heads of clients after their death in the hope of bringing them back to life in the future, when medicine has advanced. John Bischof said “There is a certain intellectual connecting of the dots that takes you from the organ to the person…I could see somebody making this argument.” But he said these ambitions were not “science-based” as unlike with organs, the person would already be dead when frozen.

Clive Coen, professor of neuroscience at King’s College London, described Kelvin Brockbank and John Bischof’s technique as “ingenious”. He said “If the technique can be scaled-up to large organs such as kidneys, the contributions to the field of organ transplantation could be immense. Such painstaking and careful research is to be applauded and must not be confused with wishful thinking about sub-zero storage and subsequent reanimation of a human body, as envisaged by the cryonics industry.”

According to NHS data, nearly 49,000 people in the UK have had to wait for an organ transplant in the past decade and more than 6,000 people, including 270 children, have died before receiving the transplant they needed.

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