Fibrin Hydrogel Containing Microvascular Fragments for Improving Subcutaneous Islet Transplants in Diabetic Rats.

摘要

OBJECTIVES: Subcutaneous tissue serves as a noninvasive and easily accessible site for pancreatic islets transplant; however, poor blood supply impedes survival of pancreatic islet cells and increases the number of islets necessary for normoglycemia. We evaluated the potential of fibrin hydrogel containing microvascular fragments to improve subcutaneous islet engraftment in diabetic rats. MATERIALS AND METHODS: Male Wistar rats were prevascularized subcutaneously for 7 days with fibrin hydrogel, 5000 microvascular fragments, or fibrin hydrogel + 5000 microvascular fragments. After streptozotocin injection to induce type 1 diabetes mellitus, 1500 IEQ were transplanted into prevascularized groups. A cotransplant group received 1500 IEQ together with fibrin hydrogel + 5000 microvascular fragments, and a control group received 3000 IEQ alone. Graft function was assessed through blood glucose monitoring, glucose tolerance tests, immunostaining, and plasma insulin concentration over 28 days. RESULTS: Immunohistochemical analysis revealed that prevascularization with the combination of fibrin hydrogel and microvascular fragments significantly increased CD31 expression compared with fibrin hydrogel alone and microvascular fragments alone (P < .05 ). Following transplantation of 1500 IEQ to diabetic rats, both the prevascularization and cotransplant groups, which received the combination of fibrin hydrogel and microvascular fragments, achieved normoglycemia within 28 days and both demonstrated superior glucose tolerance, higher plasma insulin levels, and increased CD31 and insulin expression compared with the other groups (P < .05 ). CONCLUSIONS: We demonstrated that fibrin hydrogel containing microvascular fragments could significantly increase survival and function of subcutaneously transplanted islets, allowing for effective glycemic control with reduced islet mass.