Supercooling enables long-term transplantation survival following 4 days of liver preservation

Abstract

The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

Figure 1

Transplantation of supercooled livers (a) Schematic temperature profile of the supercooling protocol. (b) Post-transplantation trends in transaminase output (shown are all recipients, including those that did not survive past day 1). (c) 30-day survival post-transplantation for selected groups.

Figure 2

Subnormothermic machine perfusion recovery and histology (a) Bile production per gram of liver during SNMP recovery phase. Survivors and nonsurvivors are separately represented for the 96 h supercooling group. * Indicates a statistically significant difference between survivors and nonsurvivors (p<0.01). (b) Hepatic resistance during SNMP recovery. (c) Hepatic transaminase levels in media during the SNMP recovery. (d) Oxygen consumption during SNMP recovery. (e) TOP: Transmission electron microscopy images (1500x initial magnification) of different stages of the supercooling protocol; fresh liver tissue, post-supercooling liver, post-SNMP recovery liver, and 30 days post-transplantation. The post-supercooling image contains a close-up of the glycogen-like structure observed in these specimens. BOTTOM: Light microscopy images of H&E stained tissue samples at corresponding stages of study.