Everyone’s seen the clichéd TV trope – White coat medical professionals rush down hospital halls cautiously clutching a plastic picnic cooler kitted out with hazard tape and covered with stickers reading ‘caution: human organ for transplant’.
It’s easy to believe that this an over-dramatised representation of the real-life transportation process for organs heading for transplant, but perhaps surprisingly, the majority of human organs around the world are still transferred between donor and recipient using a large cooler box filled with ice, with little advancement since the first successful heart transplant in the 1960s.
Despite its widespread use and broad applicability, the picnic cooler method does come with significant limitations. A heart, for example, can only be preserved for a maximum of four hours, with this figure dropping to two if surgeons want optimal transplant results. The moment a donor organ is recovered, the clock is ticking to find a recipient within a two hour radius of the donor’s hospital.
According to a 2017 study from the University of Minnesota, this results in more than 60% of donated hearts and lungs being discarded due to a lack of local suitable recipients, but if this figure could be reduced by as little as half, the US could eliminate its transplant waiting list within two years. Thankfully, there are efforts underway to improve organ transportation techniques; however, the real question is whether any innovation can trump the cost effectiveness of a small plastic box filled with crushed ice.
An altogether fishy solution
The Gibson Lab at the University of Warwick is looking into alternative cell and tissue cryopreservation techniques, motivated in part by proteins found in arctic fish that have the remarkable ability to avoid freezing in polar waters.
“We’ve been really inspired by the antifreeze proteins found in fish species. They have a property of stopping ice crystals which are formed from growing any bigger. Think of ice cream in your freezer – if you leave the ice cream from one summer to the next, then when you come and eat it its really crunchy, that’s because the ice crystals have gotten bigger – similar things can happen when you try and freeze cells and tissue.”
Gibson’s team has been trying to recreate the properties of these fish proteins in an artificial polymer, attempting to control ice crystal growth for better cryopreservation. While the process has seen success at the cellular level, unfortunately organs pose a greater challenge for cryopreservation. “We’re very interested in it,” says Gibson, “but in making this work with larger samples like tissue sections, the key challenge is getting the sample to mix through the organ and cells.”
There may well be a silver lining though. With the success Gibson’s team has seen at the cellular level, Gibson believes their technique could support future advances in ‘regenerative medicine’.
“If the dream of being able to print an organ using 3D printing of cells was to ever become a reality, you need a really good way to solve the challenge of: where do you get all the cells from?” he says. “The way we see it, if we’re able to improve that freezing process of cells, particularly stem cells, that means we’d be able to underpin some of those emerging methods.”
Thawing out a cold heart
Theoretically, if organs could be completely frozen through, they could be banked for future use, and transported to across the country – or even further afield – whenever they’re needed. Ice crystals are the problem with generic freezing techniques, so an ice-free freezing process called vitrification would ideally be the solution, but currently this technology is only available on a very small scale, and only at the cellular level.
While the freezing itself has the potential to damage tissue, the major problem is that during rewarming samples can crack or crystallise, making samples entirely unsuitable for medical purposes. But last year the University of Minnesota announced a solution using nanotechnology that could be a solution to the damaging rewarming process.
University of Minnesota mechanical engineering and biomedical engineering professor John Bischof said: “This is the first time that anyone has been able to scale up to a larger biological system and demonstrate successful, fast, and uniform warming of hundreds of degrees Celsius per minute of preserved tissue without damaging the tissue.”
Tissue, including human skin and pig heart samples, was placed in a solution that included silica-coated iron oxide nanoparticles, which when subjected to a magnetic field acted as tiny heaters, uniformly thawing the samples without any sign of damage. The technology is soon planned to be tested on rodent organs, but if it could be scaled up to human-size donor organs, banked hearts and lungs could dramatically impact donation transport and storage techniques.
Reanimating human organs
While cryopreservation certainly has wide-ranging applications and benefits, recent years have seen the emergence of alternative and altogether warmer organ preservation technique – normothermic perfusion. Current techniques only allow for ischemic storage, meaning no blood is in circulation while the organ is out of the body, and consequently cell death occurs incredibly quickly, with cold storage slowing the process. Normothermic perfusion, though, uses an altogether different technique.
Put simply the technique involves preserving an organ at normal physiological temperatures. The Organ Care System (OCS), developed by US medical technology firm TransMedics, allows organs to keep their functionality outside of the body for much greater periods of time, and even creates an environment that allows doctors to ‘reanimate’ the organ within the OCS to extend its lifespan and allow important physical assessments to be performed. “Hearts beat, lungs breathe, kidneys produce urine, livers produce bile,” says TransMedics’ website.
The OCS simulates the conditions of the human body, and blood from the organ’s donor is used to maintain blood oxygenation. The device is in use in several countries around the world, including Canada, Australia, and several European countries, and is currently under Food and Drug Administration approval with the US. Currently Transmedics have created specific organ care systems for hearts, lungs and livers.