Lessons from nature: Leveraging the freeze-tolerant wood frog as a model to improve organ cryopreservation and biobanking

The freeze-tolerant wood frog, Rana sylvatica, is one of the very few vertebrate species known to endure full body freezing in winter and thaw in early spring without any significant sign of damage. Once frozen, wood frogs show no cardiac or lung activity, brain function, or physical movement yet resume full physiological and biochemical functions within hours after thawing. The miraculous ability to tolerate such extreme stresses makes wood frogs an attractive model for identifying the molecular mechanisms that can promote freeze/thaw endurance. Recapitulating these pro-survival strategies in transplantable human cells and organs could improve viability post-thaw leading to better post-transplant outcomes, in addition to providing more time for adequate distribution of these transplantable materials across larger geographical areas. Indeed, several laboratories are beginning to mimic the pro-survival responses observed in wood frogs to preservation of human cells, tissues and organs and, to date, a few trials have been successful in extending preservation time prior to transplantation. In this review, we discuss the biology of the freeze-tolerant wood frog, current advances in biobanking based on these animals, and extend our discussion to future prospects for cryopreservation as an aid to regenerative medicine.