Fibrin Hydrogel with Microvascular Fragments Boosts Subcutaneous Islet Transplant Survival, Achieving Normoglycemia in Diabetic Rats

Current pancreatic islet transplantation for Type 1 Diabetes Mellitus (T1DM) often requires a large number of islets due to poor engraftment and survival, particularly when transplanted into subcutaneous tissue. This poor outcome is primarily attributed to inadequate vascularization and oxygen supply at the transplant site, which leads to significant islet cell death. Developing strategies to improve local blood supply and support islet viability is crucial for reducing the required islet mass and making this therapy more widely accessible and effective.

Male Wistar rats were induced with Type 1 Diabetes Mellitus using streptozotocin. They then received subcutaneous prevascularization for 7 days with either fibrin hydrogel, 5000 microvascular fragments, or a combination of both. Following this, 1500 IEQ (islet equivalents) were transplanted into the prevascularized sites. A cotransplant group received 1500 IEQ simultaneously with the fibrin hydrogel + 5000 microvascular fragments. A control group received 3000 IEQ alone. Graft function was assessed over 28 days via blood glucose monitoring, glucose tolerance tests, immunostaining for CD31 and insulin, and plasma insulin concentration measurements.

Immunohistochemical analysis revealed that prevascularization with the combination of fibrin hydrogel and microvascular fragments significantly increased CD31 expression (a marker for endothelial cells and angiogenesis) compared to fibrin hydrogel alone and microvascular fragments alone (P < .05). This indicates enhanced vascularization. Following transplantation of 1500 IEQ into diabetic rats, both the prevascularization and cotransplant groups that received the combined fibrin hydrogel and microvascular fragments achieved normoglycemia within 28 days.

These combination groups demonstrated superior glucose tolerance, higher plasma insulin levels, and increased CD31 and insulin expression compared with all other groups (P < .05), highlighting improved islet survival and function. The ability to achieve effective glycemic control with 1500 IEQ in these groups, compared to the 3000 IEQ required for the control group, suggests a significant reduction in the necessary islet mass.