Factors affecting islet graft embolization in the liver of diabetic mice.

Embolic occlusion of the portal vein due to islet transplantation is one of the major reasons for reduced survival of transplanted islets. In this study, we examined the location of islets as well as the correlation between islet and portal vein size after intraportal islet transplantation, and evaluated liver and islet pathology. BALB/c mice were intraportally transplanted with 800 islets and the liver was examined at postoperative day (POD) 0 (n=7), POD 2 (n=4) and POD 28 (n=3). Liver specimens were stained for hematoxylin and eosin (necrosis), insulin, and TUNEL (apoptosis). We evaluated distance from liver surface to islets, islet and portal vein diameter, embolic ratio (islet diameter/portal vein diameter), apoptosis/necrosis of islets and apoptosis/necrosis of the liver tissue surrounding the islet. The liver was divided into peripheral and central sites. Islet and liver apoptosis/necrosis were significantly higher at peripheral sites. In regions without liver apoptosis or necrosis, portal vein diameter was significantly larger and embolic ratios were significantly lower. Transplanted islets and liver tissue exhibited more injury at peripheral sites, in part, due to smaller diameters of portal venules that result in more frequent emboli following islet transplantation.