Improvement of Graft Survival by Surface Modification With Poly(ethylene glycol)-Lipid and Urokinase in Intraportal Islet Transplantation

Background. Transplantation of pancreatic islets of Langerhans (islets) has been successfully used to treat insulin-dependent diabetes mellitus. However, it remains an experimental procedure, and some technical aspects should be improved. Among these issues, early graft loss induced by instant blood-mediated inflammatory reactions (IBMIR) is an urgent obstacle to overcome. Coating of islet surface with bioactive molecules has been studied as a method to inhibit IBMIR. Methods. Poly(ethylene glycol) (PEG)-lipid or PEG-urokinase was immobilized onto islets through hydrophobic interaction and DNA hybridization. Efficacy of surface modification for the inhibition of IBMIR was evaluated using a syngenic mouse transplantation model. Outcomes evaluated were blood insulin levels immediately after transplantation, blood glucose levels, and histochemical analyses of transplanted islets within the liver. Results. Insulin level sharply increased after transplantation in recipient mice with naive islets but remained low in recipients with surface-modified islets. A total of 250 naive islets or 125 modified islets were needed to normalize blood glucose levels of the diabetic mouse model. These results indicate that surface modification of islets effectively protects against IBMIR. Conclusion. Surface modification of islets with PEG-lipid or PEG-urokinase is a potential useful technology in the clinical application of islet transplantation.