Adenovirus Mediates CTLA-4Ig Gene Local Transfer To Inhibit The Acute Rejection Of Composite Tissue Allograft In Rats

Objective: To observe the effect of CTLA-4Ig gene transfer delivered by adenovirus to inhibit the acute rejection of composite tissue allograft (CTA) in rat.Methods: The CTA model was established by transplanting the epigastric flaps harvested from Brown Norway rats into recipients of Lewis rat. 30 couples of recipients were randomly divided into 3 groups equally: Group A is control group, and the transplanted epigastric flaps were perfused with PBS solution containing no adenovirus. Group B is negative control group, and the transplanted epigastric flaps were perfused with PBS solution containing adenovirus. Group C is gene therapy group, and the transplanted epigastric flaps were perfused with PBS solution containing AdCTLA-4Ig. The survival days and rejection time of transplanted flap were observed, and histopathologic observation was conducted. The expression of CTLA-4Ig in the transplanted tissue and its inhibit effect on acute rejection were also examined. Results: The average survival days of flap grafts in group A and group B were (7.8±1.5) days and (7.1±1.6) days, respectively. In contrast, the survival days of flap grafts in group C was (10.4±2.3)days, which was longer than that in group A and group B, the difference was statistically significant(P<0.01). histopathologic outcomes showed that severe acute rejection occurred 7 days after the transplantation in all three groups, but the rejection in group C is milder than the other two groups. The serum level of IL-2 elevated significantly in the early stage after the transplantation in all three groups. However, the serum level of IL-2 in group C is lower than that in the other two groups significantly (P<0.01) in the 3rd and 7th day after the transplantation.Conclusion: A novel Composite tissue allograft transplantated gene transfection model was established. Using ex vivo gene transfer technique, CTLA-4Ig gene can be introduced into the flap graft under the condition of physiological temperature, and the CTLA-4Ig gene was expressed in the transplanted tissue. The acute rejection versus transplanted flaps can be inhibited by the CTLA-4Ig and the survival days of transplanted flaps can be prolonged.