Improving Pancreatic Islet Transplantation Using Fibrin Hydrogel Containing Microvascular Fragments in Subcutaneous Tissue of Type I Diabetic Rats

Abstract Objective(s): Islet transplantation offers a promising treatment for Type 1 diabetes mellitus (T1DM). Subcutaneous tissue is a non-invasive site, but it has poor blood supply and requires more islets to achieve normoglycemia. We assessed the impact of fibrin hydrogel containing microvascular fragments (MVF) on the vascularization of subcutaneous tissue using two approaches: prevascularization (prior to islet transplantation) or co-transplantation (simultaneously with islet transplantation). Materials and methods: Wistar rats were prevascularized subcutaneously for 7 days with fibrin (H), 5000 MVF, or fibrin + 5000 MVF (HMVF). After streptozotocin injection to induce T1DM, 1500 islet equivalents (IEQ) were transplanted into prevascularized groups. A co-transplantation group received 1500 IEQ and HMVF (Co-HMVF1500), and a control group received 3000 IEQ alone (Islet only 3000). Graft function was evaluated through blood glucose monitoring, glucose tolerance tests, immunostaining, and plasma insulin concentration over 28 days. Results: HMVF-prevascularized group presented significantly more CD31-positive cells compared with those from H- or MVF-prevascularized groups (p<0.05). Prevascularization and co-transplantation approaches using HMVF resulted in normoglycemia with a reduced islet mass (1500 IEQ) compared with those in the Islet only3000, H1500, and MVF1500 groups. In addition, both the HMVF1500 and Co-HMVF1500 rats indicated superior islet survival and function, compared with the H1500, MVF1500, and Islet only3000 groups, as evidenced by increased CD31-positive cells and insulin-positive cells, improved glucose tolerance, and elevated plasma insulin concentrations (p<0.05). Conclusion: Fibrin hydrogel containing MVF could significantly increase the survival and function of subcutaneously transplanted islets, allowing for effective glycemic control with a reduced islet mass.