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김민준,Zahid Alam,오언주,황용화,이용규,윤채옥,이동윤 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.47 No.-
Pancreatic islet transplantation is a promising strategy for diabetic patients. Unfortunately, host’simmune cells rapidly reject transplanted islets. Cytoprotective gene therapy has been tried to protectthem. However, the transduce yield of ex vivo gene delivery into islets is very rare due to the anatomicalstructure of them. Therefore, we newly designed an Arg-Gly-Asp (RGD) peptide-incorporated adenovirusvector expressing cytoprotective heme oxygenase-1 (HO1) gene (RGD-Adv-HO1) for effective genetherapy to islets via RGD–integrin interaction between adenovirus and islet. After exposure to islets, thetransduced RGD-Adv-HO1 did not affect the viability and insulin secretion of islets with highertransduction efficacy. Moreover, HO1 showed cytoprotective effect from the presence of paraquat-induced reactive oxygen species (ROS). When the transduced islets were xenotransplanted intostreptozotocin-induced diabetic Balb/c mice, their survival time in vivo was significantly prolonged withcuring blood glucose level, which was attributed to the stable expression of HO1. Additionally, we foundthat RGD-Adv-HO1 showed a good synergistic effect in xenotransplanted islets when accompanied withlow dose of immunosuppressants tacrolimus and anti-CD154 monoclonal antibody. Collectively, this newcombinatorial remedy of RGD-Adv-HO1 transduction with low dose of immunosuppressive agents couldbe an effective therapy for successful outcome of islet transplantation