Organ shortage crisis for transplants could be solved with less toxic cryoprotectants

Proline and glycerol can keep cells from freezing, preserving cells and perhaps one day organs for transplant.

Those sharp edges make ice crystals lethal to cells, but cryoprotective agents prevent this, and better ones have just been found (structure pictured here). Image Credit: Saffron Bryant

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 higher-profile applications are still some way off.

The formation of ice crystals destroys cells, whose delicate functioning is not well suited to spiky structures. Sometimes, however, cells need to be cooled to keep them alive, which is done with cryoprotective agents. An announcement in the Journal of Materials Chemistry B that certain combinations of agents are less toxic and more effective than their components could represent a breakthrough.

The imbalance between people who need organ transplants and donated organs has led to many proposed solutions. Advances in artificial hearts and transgenic pigs capable of producing human-compatible organs, and there are always efforts to increase donation rates. However, simply being able to store organs a bit more might make them unnecessary.

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

“Cryoprotectants stop ice formation, which leads to a glassy structure that can solidify but doesn’t cause the same kind of damage as ice crystals.” Bryant said in a statement.

The problem, he explained to IFLScience, is that the existing versions are also toxic to cells and can’t even get into some. Even for the cell types they work on, too much can be fatal. “Organs have a depth problem,” he told IFLScience. “If you expose the cells to the outside, by the time the agent has reached the inside cells, the outside cells will be 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 cryoprotectants (right) viewed using a frozen atomic force microscope Credit: Aaron Elbourne

For 50 years, most cryoprotection has been done with dimethyl sulfoxide and glycerol. Bryant and his co-authors discovered that when combined with the amino acid proline, glycerol becomes more effective and less toxic in four types of cells, allowing it to be applied at body temperature for much longer before freezing.

As urgent as the need is, Bryant doesn’t plan to jump right into trying to preserve organs. “Our first step is to try to freeze platelets, which can currently only be stored for 5 to 7 days,” she told I:FLScience. “It should be pretty easy in theory, but it’s not currently possible. From there, we want to move on to other cell types, including stem cells, and then to more complex systems.”

Neurons frozen with new cryopreservatives survive the process

Microscope image of neural cells after freezing them in the team’s new cryoprotectant, a mixture of proline and glycerol. Image Credit: Saffron Bryant

Nature has already created a large number of cryopreservative agents, developed for plants and animals that survive harsh winters. However, Bryant pointed out, animals like wood frogs make them within their own cells; introducing them into human cells is much more difficult.

Bryant said finding the right agents involves a lot more trial and error than he’d like. First, though, the team looks for chemicals that meet three criteria; it is known to suppress ice crystal formation, the ability to enter human cells, and low toxicity.

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