The current clinical standard in tissue preservation, static hypothermic preservation (HP) in ice-cold preservation solution (+4°C), is insufficient to preserve tissue viability for more than a few hours, creating a technological bottleneck to realizing tolerance protocols in VCA transplantation.
We recently developed a novel sub-zero non-freezing (SZNF) protocol that enables viable preservation of rat livers for 3 days with 100% post-transplant survival, three times the maximum possible with current clinical standard, HP . Our method relies on i) the use of supercooled temperatures below freezing point (-6°C) to slow metabolism while avoiding freezing injury, ii) preservative agents (PEG and 3OMG), and iii) a rewarming step with 21°C subnormothermic machine perfusion (SNMP), which ameliorates some of the cold ischemic injury. More recently, utilizing DoD RTRP funding (W81XWH-17-1-0680), we developed a machine perfusion protocol for rodent hind limbs, and were able to preserve rat limbs that were supercooled for 24hrs in a viable state. These technologies provide our group unique readiness to extend “revolutionize ex vivo VCA tissue preservation strategies to extend the timeline between procurement and transplantation”, as well as test its utility to enable tolerance induction in a clinically relevant large animal model.
Our objective is to extend tissue preservation for 3 days, and that this the extended preservation time will enable utilization of tolerance induction protocols with a schedule that would be realistic for clinical implementation.