Solving Donor Organ Shortage with Insights from Freeze Tolerance in Nature: Activating endogenous antioxidant systems with non-coding RNA to precondition donor organs

The North American wood frog, Rana sylvatica, endures seasonal whole-body freezing during the winter and thawing during the spring without sustaining any apparent damage from ice or oxidative stress. Strategies from these frogs may solve the shortage of human donor organs, which is a multidisciplinary problem that can be alleviated by eliminating geographical boundaries. Rana sylvatica deploys an array of molecular and physiological responses, such as glucose production and microRNA regulation, to help it survive the cold. These strategies have been adapted in the lab to impart cryotolerance in liver cells, and the non-freezing supercooled storage of transplantable rat livers - milestones that have advanced the field toward cryopreserving human donor organs in the clinic. In this review, a case is presented for the use of non-coding RNAs to decrease oxidative damage of donor organs by activating endogenous antioxidant systems prior to procurement.