Adenovirus-mediated gene transfer of triple human complement regulating proteins (DAF, MCP and CD59) in the xenogeneic porcine-to-human transplantation model

Transplant International - Tập 15 - Trang 212-219 - 2002
Masayuki Shiraishi1, Takashi Oshiro1, Eiji Nozato1, Masayoshi Nagahama1, Kaoru Taira1, Hironori Nomura1, Hideki Sugawa1, Yoshihiro Muto1
1First Department of Surgery, University of the Ryukyus, School of Medicine, Uehara 207, Nishihara-cho, Okinawa 903-0215, Japan

Tóm tắt

In this study, the adenovirus-mediated gene transfer of triple human complement regulating proteins was investigated in xenogeneic pig liver perfusion. The porcine liver was perfused in situ at 4 °C under a pump-driven veno-venous shunt of the portal vein and inferior vena cava, with 5 to 15×1011 plaque-forming units (pfu) of adenovirus vector (group 1: AxCALacZ; 2: AxCACD59; 3: AxCACD59 + AxCADAF; 4: AxCACD59 + AxCADAF + AxCAMCP) for 1 h (for each, n=3). The livers were harvested 24 h after gene transfer and then were reperfused ex-vivo with fresh human blood for 2 h. In immunohistochemical staining, each complement regulating protein (CRP) showed a distribution similar to that of the LacZ expression. The C3 levels in the perfusate were also maintained at higher levels in group 4 from 60 to 120 min after reperfusion (C3: 85% to 95% of the initial level) than in groups 1 to 3 (C3: 80% to 90% of the initial level) from 60 to 120 min after reperfusion. The complement deposition on the porcine liver [C3, membrane attack component (MAC)] decreased significantly more in group 4 than in groups 1 to 3. In conclusion, the adenovirus-mediated multiple gene transfer of human CRPs (hCRPs) was found to effectively suppress the complement activation in xenogeneic pig liver perfusion.