Prolongation of Islet Graft Survival Using Concomitant Transplantation of Islets and Vascular Endothelial Cells in Diabetic Rats

Abstract

Background The transplantation of isolated islets of Langerhans is nearing acceptance as treatment of type 1 diabetes mellitus. Because the arterial and venous connections of the pancreas are disrupted during islet isolation, islets must be revascularized after transplantation. Objective To observe whether increased numbers of vascular endothelial cells in islets can affect the angiogenesis and function of the grafts. Materials and Methods Rats with streptozocin-induced diabetes were divided into 3 groups. The rats in group 1 received islet grafts under the capsule of the left kidney; rats in group 2 received combined vascular endothelial cell and islet transplants; and rats in group 3 served as controls. After the transplantation procedure, blood glucose and insulin concentrations were evaluated daily. Hematoxylin-eosin and immunohistochemical staining was used to detect expression of vascular endothelial growth factor antibodies in the diabetic rat kidneys. The mean microvascular density was also calculated. Results At 3 days posttransplantation, blood glucose and insulin concentrations returned to normal in group 2, however, they declined only slightly in group 1, and moderate hyperglycemia was present. There was a significant difference in blood glucose and insulin concentrations between the 2 groups after 3 days ( P < .05). The mean (SD) microvascular density in group 2 was markedly higher than that in group 1 (12.58 [1.81] vs 10.38 [0.97] P = .04). Conclusion This study suggests that concomitant transplantation of isolated islets with endothelial cells can prolong islet graft survival in diabetic rats.