초록 |
Recently, we have developed the PEGylated islets, surface modification of islet with PEG, to reduce immunogenecity of islets. Several studies show that the heme oxygenase-1 (HO-1) can show the anti-inflammation effect by acting antioxidant products degraded from heme. Therefore, the goal of this study was to evaluate hypothesis that the HO-1 expressing PEGylated islets could be synergistically protected from graft rejection. Isolated islets were reacted with PEG to bind PEG onto islet surface. Then, PEGylated islets were allotransplanted in diabetic rats, and 1 mg/kg/day of cyclosporine A (CsA) was daily injected or not. To induce HO-1 expression, 10 mg/kg/day cobalt chloride (CC) was subcutaneously administered in the recipients for 6 day. After PEGylated islet transplantation with CC or CC plus CsA, their median survival time was 12 or more than 100 days, respectively (n=7). Interestingly, the histology data of the case of CC plus CsA showed that insulin- and HO-1-positive islets were well present in the whole are of transplantation site. However, for nonmodified islet (control) transplantation, they were completely rejected within 10 days in all cases. This study suggests that the HO-1 expression with or without CsA regimen can significantly improve the transplanted PEGylated islet survival. |