Modification of donor MHC antigens with antisense gene transfer to prevent rejection of transplanted organ, and mechanism of hepatic sinusoidal endothelial cell proliferation during regeneration after partial hepateclomy.

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In our first study, we examined whether insertion of an antisense vector into the allograft could down-regulate the expression of the target antigens and to prevent the rejection of transplanted organs. Down-regulation of' donor MHC class I antigen expression on the donor cells Was observed after transfection of plasmid vector containing antisense of donor target antigen in vitro, and also immunological response to these cells decreased. However, in vivo, efficient transfection of plasmid vector containing antisense to the donor graft liver during cold preservation periods was verry difficult at present. Now we are developing new technology to provide for efficient in vivo transfection.In our second study, We investigated expressions of vascular endothelial cell growth factor (VEGF) and its receptors, flt-1 and -KDR/flk-1 in regenerating liver after 70 % hepatectomy. Proliferation of both hepatocytes and SECs was also monitored by evaluating proliferating cell nuclear antigen (PCNA) labeling index. The expression of VEGF mRNA was increased markedly between 48 and 72 hr after hepatectomy. The immunohistochemical staining revealed that expression of VEGF started to increase 24 hr after hepatectomy, with a peak at 72 hr, and the majority of the VEGF-positive cells were hepatocytes. Meanwhile, expression of flt-1 and KDR/flk-1 was observed along the sinusoids even before hepatectomy, but was increased between 72 and 120 hr. These results strongly suggest that VEGF secreted by proliferating hepatocytes may represent an important stimulator of SEC proliferation.