title: Surface modification of pancreatic islets using heparin-DOPA conjugate and anti-CD154 mAb for the prolonged survival of intrahepatic transplanted islets in a xenograft model.
abstract: This study proposes a combination method of using 3,4-dihydorxy-l-phenylalanine (DOPA) conjugated heparin (heparin-DOPA) and a low dose of anti-CD154 monoclonal antibody (MR-1) treatment to improve the survival time of intrahepatic islet xenograft. To inhibit instant blood mediated inflammatory reactions, heparin-DOPA was directly grafted to the pancreatic islet surface. The surface coverage of heparin-DOPA, the viability and functionality of heparin-DOPA grafted islets were evaluated. In addition, the combined effect of grafted heparin-DOPA and a low dose of MR-1 (a T-cell targeting immunosuppressive drug) on the survival of islet was evaluated in a xenograft model. Both unmodified islets and heparin-DOPA grafted islets were completely rejected within 2 weeks after intraportal transplantation. However, when 0.1 mg/mouse of MR-1 was administered (at day 0, 2, 4, 6 of transplantation) to 11 mice that had heparin-DOPA grafted islets transplanted to, seven out of the recipients maintained normoglycemia over 60 days. Therefore, we propose that a developed combinatory immunoprotection protocol of surface modification of pancreatic islets using heparin-DOPA with a low dose of MR-1 can be effective in prolonging the survival rate of transplanted islets in a xenograft model.
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors: Yoon Suk
authors: YS
authors: Jung
authors: Jee-Heon
authors: JH
authors: Jeong
authors: Simmyung
authors: S
authors: Yook
authors: Bok-Hyeon
authors: BH
authors: Im
authors: Jinwon
authors: J
authors: Seo
authors: Sung Woo
authors: SW
authors: Hong
authors: Jun-Beom
authors: JB
authors: Park
authors: Victor C
authors: VC
authors: Yang
authors: Dong Yun
authors: DY
authors: Lee
authors: Youngro
authors: Y
authors: Byun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D023201:CD40 Ligand / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000737:chemistry*; D006085:Graft Survival / Q000187:drug effects; D006493:Heparin / Q000737:chemistry*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D001672:Biocompatible Materials; D023201:CD40 Ligand; D004295:Dihydroxyphenylalanine; D006493:Heparin