Study on Strategies for Non-Heart Beating Liver

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Sinusoidal endothelial cell (SEC) injury is a major abnormality in the liver transplanted from non-heart beating donors. It is important to protect SECs for the establishment of non-heartbcating liver transplantationVEGF is a factor essential for maintenance as well as proliferation of SECs in primary culture. We demonstrated that VEGF also acted as avascular permeability factor through up-regulation of the porosity on SECs. Furthermore, VEGF inhibited contraction of stellate cells, pericytes of SECs, suggesting that VEGF can regulate microcirculation in the hepatic sinusoids. VEGF expression in hepatocytes was increased in rat liver after cold preservation in UW solution, but mRNA expressions of VBGFR-1 and VEGFR-1 were decreased prior to the development of SEC in jury These results may suggest that VEGF cannot work effectively on SECs in the cold preserved liver, and also that exogenous VBGF cannot prevent SEC from injuryKupffer cells were markedly activated in the cold preserved liver, and this activation contributed to SEC injury after orthotopic transplantation of such livers. We found that activated Kupffer cells expressed osteopontin an essential cytokine for initiation of Th1 immune response. Also, we demonstrated that osteopontin played a major role as a chemokine in macrophage migration into the liver using mice with different alleles of osteopontin gene, suggesting that the modulation of osteopontin expression in Kupffer cells may be another strategy for protection of the SECs. We made transgenic mice expressing osteopontin very highly in the liver using human serum amyloid P component promotor as a vector specific for hepatocytes Investigations to prove our hypothesis are now in progress