ESTABLISHMENT OF NEW IMMUNOSUPPRESSIVE STRATEGY USING GENE TRANSFECTION TECHNIQUE

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It has been reported that endothelial cell activation and apoptosis induced by xenoantibody may play a major role in concordant xenograft rejection as well as direct cell destruction by xenoantibody. Thus, prevention of endothelial cellular apoptosis may prevent graft coronary atheroscrelosis (GCAS). In the present study, the effects of gene transfection of cytoprotective gene, Bcl-2 in graft survival and GCAS was investigated in a hamster-to-rat cardiac transplant (HTx) model in which the recipients were treated with FK506 and cobra venom factor (CVF) to block complement and cellular type rejection.【Material and Method】 14 Golden Hamster hearts were transplanted into Lewis rat abdomen using Ono-Lindsey methods. All rats were given CVF (0.2 mg/Kg ; day 0 and 1) and FK506 (1 mg/Kg from day 0) intramuscularly. These hearts were divided into two groups. In Group-B (+) and -B (-), grafts were transfected by perfusing coronary artery with HVJ-liposome containing vector with Bcl-2 gene and only vector, respectively. Rejection was defined by cessation of palpation from outside. The explanted grafts were evaluated by H-E staining and immunohistochemical staining of Bcl-2.【Results】 Graft survival was not significantly different in these groups. Bcl-2 was expressed only in the graft of Group-B (+) within 3 weeks after HTx. Although GCAS score in Group-B (-) was significantly higher than that in Group-B (+), there was no difference between those more than 4 weeks after HTx.【Conclusion】 Although there was no significant difference in graft survival between both groups, these data suggested that gene transfection of Bcl-2 may prevent endothelial cell activation resulting in preventing graft coronary astheroscrelosis in concordant xenografts.