High sub-zero organ preservation: A paradigm of nature-inspired strategies

Abstract

In recent years there have been several advancements in organ preservation that have yet to see widespread clinical translation. While static cold storage (SCS) at 2 °C-4 °C continues to be the state-of-the-art strategy, it contributes to the current shortage of transplantable organs due to the limited preservation times it affords combined with the limited ability of marginal grafts to tolerate SCS. The era of optimizing storage solutions to minimize SCS-induced hypothermic injury has largely plateaued in its improvements, resulting in a shift towards the use of machine perfusion systems to provide continuous metabolic support, or the use of sub-zero storage temperatures to leverage the protection brought forth by a reduction in metabolic demand. Many of the rigors that organs are subjected to at low sub-zero temperatures (-80 °C to -196 °C) commonly used for mammalian cell preservation have yet to be surmounted, and therefore the focus of this article lies on an intermediate range of storage temperatures (0 °C to -20 °C) where much success has been seen in the past two decades. Numerous mechanisms leveraged by organisms capable of withstanding prolonged periods at these temperatures through either avoiding or tolerating the formation of ice has provided a foundation for some of the more promising efforts, and thus we aim to contextualize the translation of these nature-derived strategies to mammalian organ preservation.

Keywords: Antifreeze proteins; Ex vivo perfusion; Freeze avoidance; Freeze tolerance; Hypothermia; Ice recrystallization; Isochoric preservation; Metabolic preconditioning; Organ banking; Supercooling.