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Novel organ preservation methods: not only cool but supercool!

E supercooling enables, at least in theory, substantially longer preservation times with many advantages including optimized donor-recipient combinations and improved transplant outcomes. Although most research groups interested in improving organ preservation have focused on developing hypoor normothermic perfusion concepts in the recent past, others decided to swim against the current, applying the concept of supercooling that is routinely used for the storage of single cells and tissues to the preservation of whole livers. The ingenuity of this particular approach had been based on the experience in cryopreservation translated into a whole organ preservation concept. The authors convincingly show that supercooling is only effective when preceded by a preparation and followed by a resuscitation protocol. This 4-step approach consisted of a loading phase at 21°C, a controlled cooling phase to 4°C, a supercooling phase to −6°C, and a final recovery phase at 21°C. The first step to apply effective supercooling includes loading of cells with permeable cryoprotectant agents (PCAs) commonly used during cryopreservation of cells. The authors' choice for 3-O-methyl-glucose (3-OMG) as an effective permeable cryoprotectant agents derived from the observation that freeze-tolerant frogs like Rana sylvatica mobilize high amounts of glucose during freezing, thus resisting temperatures up to −16°C. The 3-OMG cannot be metabolized and accumulates thus in liver cells, thereby increasing intracellular glucose levels that are necessary to sustain supercooling.Of interest, frogs do not only have elevated glucose levels during freezing but also increased urea levels, explaining their ability to sustain even lower temperatures.