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Health and Medicinemedicine

Transplant Organ Shortage Crisis Could Be Solved With Less Toxic Cryoprotectants

Around 60 percent of donated hearts and lungs are thrown away because they can't be transplanted in time, but improved cryoprotecting agents could provide the solution.

author

Stephen Luntz

Freelance Writer

clockJun 22 2022, 11:06 UTC
Proline and glycerol can save cells from freezing, preserving cells and maybe someday organs for transplantation
Those sharp edges make ice crystals lethal for cells, but cryoprotecting agents prevent this, and better ones have just been found (structure depicted here). Image Credit: Saffron Bryant

The chemicals used for decades to prevent cell damage from freezing don't work for organs (or even many cell types), and the cost is measured in thousands of lives. The discovery of less toxic agents could change that – although the highest-profile applications are still a fair way off.

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Ice crystal formation destroys cells, whose delicate workings don't cope well with spiky structures. Sometimes, however, it is necessary to cool cells down to keep them alive, which is done using cryoprotecting agents. An announcement in the Journal of Materials Chemistry B that certain combinations of agents are less toxic and more effective than their constituents could represent a major breakthrough.

The imbalance between people needing organ transplants and donated organs has led to many proposed solutions. Progress is being made on artificial hearts and genetically engineered pigs capable of producing human-compatible organs, and there are always efforts to boost donation rates. However, just being able to store organs a little longer might make these unnecessary.

Dr Saffron Bryant of Australia's RMIT told IFLScience that the Organ Preservation Alliance has calculated that by saving just half the donated hearts and lungs currently thrown away in the United States, the waiting list for those organs would be eliminated. These organs are not abandoned because they are not up to scratch, but because they can't be transferred to a recipient in the few hours available. “I was surprised when I looked into it,” Bryant added.

“Cryoprotectants stop ice forming, leading to a glassy structure instead that can solidify but doesn't cause the same sort of damage as ice crystals.” Bryant said in a statement

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The problem, she explained to IFLScience, is existing versions are also toxic to cells, and can't even get inside some. Even for those cell types where they work, too much can be fatal. “Organs have a depth problem,” she noted to IFLScience. “If you expose the cells on the outside, by the time the agent has reached the inner cells the outer ones are dead.”

Atomic force microscope images of a neural cell after freezing using the standard method (left) and the team’s new method (right).
A neuron frozen using traditional methods (left) and the new cryoprotectors (right) as seen using an atomic force microscope frozen Credit: Aaron Elbourne


For 50 years, most cryoprotection has been done with dimethylsulfoxide and glycerol. Bryant and co-authors found that when combined with the amino acid proline, glycerol becomes more effective and less toxic on four types of cells, allowing application at body temperatures for much longer prior to freezing.

Urgent as the need is, Bryant isn't planning to jump straight to trying to preserve organs. “Our first step is to try to freeze platelets, which can currently only be stored for 5-7 days,” she told I:FLScience. “It should be quite easy in theory, but it's not currently possible. From there we want to move onto other cell types, including stem cells, and then to more complex systems.”

Neurons frozen with new cryopreservers survive the process
Microscope image of neural cells after freezing with the team’s new cryoprotectant, a mixture of proline and glycerol. Image Credit: Saffron Bryant


Nature has already created a wealth of cryopreserving agents, evolved for plants and animals that survive bitter winters. However, Bryant noted, animals such as wood frogs produce these inside their own cells; getting them into human cells is much harder.

Bryant said finding suitable agents involves much more trial and error than she would like. First, however, the team seek chemicals meeting three criteria; being known to suppress ice crystal formation, capacity to get inside human cells, and low toxicity.


Health and Medicinemedicine
  • medicine,

  • ice,

  • organ transplant,

  • cryopreservation

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