Development of the supercooling preservation method for transplant liver graft and analysis of the mechanism of cold preservation injury

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Supercooling is likely to achieve superior preserability of graft organs. In order to improve the preservation procedure of liver grafls, we attempted the subzero nonfreezing (SZNF) storage methods. In consideration of applying the SZNF storage to clinical use, we employed anti-nucleating protein (ANP), isolated from bacterium^1, as anti-freezing agent (AFA) for the prevention of concussive organ freezing.Recent studies showed that the sinusoidal endothelial cell (SEC) damages are the primary targets in cold preservation/ reperfusion injury and the apoptosis of SECs plays a critical role. For protection of SECs against supercooling preservation injury, we used ascorbic acid 2-glucoside (AA-2G) as antioxidant which is chemically stable ascorbic acid derivative.In this research, we investigated the participation of SECs apoptosis in supercold iscbemic injuiy and the efficacy of the SZNF liver storage using ANP with AA-2G in the University of Wisconsin (UW) solution.In our previous study the SZNF storage of isolated SECs failed to show hs advantages as compared with hepalocytes(HC). The problem to be solved for the SZNF liver storage is the stronger hypothermia-specific damage enhanced by supercooling. In this study the SZNF condition by itself could not achieve the better preservavility of HCs in transplanted liver due to the microcirculatoiy disturbance by SECs damage.The reactive oxygen species and free radicals appeared to play an important role in apoptosis of SECs upon cold ischemia / reperfbsion injury. The usage of AA-2G as a free radical scavenger reduced the sinusoidal damages and inhibited apoptosis in SECs enhanced by supercooling. The protective effect of AA-2G against SECs damage led to the better preservavilily of HCs as a consequence of supercooling storage in transplanted liver.The SZNF liver storage with ANP and AA-2G had a potency to surpass the conventional cold preservation