Highly Selective Intraportal Transplantation of Pancreatic Islets

Abstract

Histological assessment of intraportally transplanted islets in experimental rodent models is limited by the wide dissemination of islets throughout the liver. We describe a technique of highly selective intraportal islet transplantation, which increases the density of transplanted islets and hence facilitates their histological analysis and validate this model as a means of quantitative histological analysis of islet graft survival. We also compared the number of islets visualized histologically with that of nonabsorbable dextran beads, representing the number of transplanted islets there would have been if there had been no graft loss. Diabetic Lewis rats or nondiabetic Sprague-Dawley rats were transplanted with 500 or 1000 syngeneic islets or an equivalent number of beads either into the main branch (MB), or selectively into the right branch (RB) of the portal vein. Islet transplantation led to an identical fall in blood glucose levels whichever technique was used. The graft area and number of islets recovered for histological analysis was 3- to 4-fold higher when islets were transplanted using the RB technique. Quantitative histological graft analysis demonstrated that 46% to 61% of intraportally transplanted islets were lost compared with corresponding bead graft sizes. Fewer islets were lost when a greater islet mass was transplanted. Selective islet transplantation increases the concentration of islets and hence facilitates islet recovery after intraportal transplantation without detrimental effects on transplantation outcome. This technique, when combined with bead transplantation and digital image analysis, provides an accurate method for estimating the number of islets surviving intra-portal transplantation.