Cobalt-protoporphyrin treatment enhances murine isoislets engraftment

Abstract 

To study the effect of treatment with cobalt-protoporphyrin (CoPP) for the induction of the heme oxygenase-1 (HO-1) enzyme on islet engraftment donor mice received either a single intraperitoneal injection of CoPP (20 mg/kg body weight) 1 day prior to islet isolation or this injection plus a 9 day posttransplantation course of Copp. After a single injection of CoPP, the CoPP-induced islets contained higher HO-1 proteins than did the normal islets both at 12 (5.3 ± 1.5 vs 0.1 ± 0.1 ng/mg protein, P < .01) and at 30 hours (6.8 ± 2.1 vs 0.4 ± 0.3 ng/mg protein, P < .05), but not at 56 hours (1.9 ± 0.8 vs 1.6 ± 0.8 ng/mg protein, P > .05). In contrast, diabetic mice that received 75 CoPP-induced islets and a 9-day CoPP injection course posttransplantation showed better improvement in blood glucose levels and body weights than did the mice that only received CoPP-induced islets. Mice of both CoPP-treated groups displayed better improvement in glycemic control than mice that received control islets. At 8 weeks after transplantation, the insulin content of grafts from both CoPP groups was significantly higher than that in the control group. In conclusion, CoPP treatment for the induction of HO-1 enhances engraftment of islets in a syngeneic murine transplantation model.