A Hibernation-Like State for Transplantable Organs: Is Hydrogen Sulfide Therapy the Future of Organ Preservation?

Abstract

Significance: Renal transplantation is the treatment of choice for end-stage renal disease, during which renal grafts from deceased donors are routinely cold stored to suppress metabolic demand and thereby limit ischemic injury. However, prolonged cold storage, followed by reperfusion, induces extensive tissue damage termed cold ischemia/reperfusion injury (IRI) and puts the graft at risk of both early and late rejection. Recent Advances: Deep hibernators constitute a natural model of coping with cold IRI as they regularly alternate between 4°C and 37°C. Recently, endogenous hydrogen sulfide (H 2 S), a gas with a characteristic rotten egg smell, has been implicated in organ protection in hibernation. Critical Issues: In renal transplantation, H 2 S also seems to confer cytoprotection by lowering metabolism, thereby creating a hibernation-like environment, and increasing preservation time while allowing cellular processes of preservation of homeostasis and tissue remodeling to take place, thus increasing renal graft survival. Future Directions: Although the underlying cellular and molecular mechanisms of organ protection during hibernation have not been fully explored, mammalian hibernation may offer a great clinical promise to safely cold store and reperfuse donor organs. In this review, we first discuss mammalian hibernation as a natural model of cold organ preservation with reference to the kidney and highlight the involvement of H 2 S during hibernation. Next, we present recent developments on the protective effects and mechanisms of exogenous and endogenous H 2 S in preclinical models of transplant IRI and evaluate the potential of H 2 S therapy in organ preservation as great promise for renal transplant recipients in the future. Antioxid. Redox Signal. 28, 1503–1515.