title: Cell surface modification by activated polyethylene glycol prevents allosensitization after islet transplantation.
abstract: The necessity to transplant islet tissue without the need for immunosuppressant therapy has led to the development of materials for immune modulation. Pegylation makes islets antigenically silent, protecting them from the adsorption of foreign protein and thus avoiding immune injury. The aim of this study is to determine whether pegylation of islets prolongs islet survival and function both during tissue culture and posttransplantation. We used cyanuric chloride-activated methoxy-polyethylene glycol for cell surface modification. To detect the pegylation effect on splenocytes, we measured antibody binding inhibition and abrogation of lymphocyte proliferation. To detect the pegylation effect on islet grafts, we performed rodent islet transplantation. Islet viability and function were maintained after pegylation. Pegylated islets showed a 90% decrease in antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte culture. However, when pegylated islets were transplanted, no prolongation of graft survival was observed. When a subtherapeutic dose of immunosuppressant was given at the time of transplantation of pegylated islets, islet graft survival was significantly prolonged. In addition, when rats were sensitized with donor splenocytes, graft survival was prolonged by pegylation. We observed that pegylation of islets, combined with a subtherapeutic dose of immunosuppressant, protects the graft from rejection. Prolonged graft survival in sensitized recipients showed that pegylation of islets shifted the pattern of rejection from an acute humoral response to a less aggressive cellular alloresponse.
authors.affiliation: Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Seoul, 138-736, Korea.
authors.forename: Yu-Mee
authors.initials: YM
authors.lastname: Wee
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Lim
authors.forename: Yang-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Song-Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: EunSil
authors.initials: E
authors.lastname: Yu
authors.forename: Myung-Ok
authors.initials: MO
authors.lastname: Park
authors.forename: Monica Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Hyuk-Jai
authors.initials: HJ
authors.lastname: Jang
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Myung-Hwan
authors.initials: MH
authors.lastname: Cho
authors.forename: Duck-Jong
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D006084:Graft Rejection / Q000517:prevention & control*; D007165:Immunosuppression Therapy / Q000379:methods; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013311:Streptozocin; D013499:Surface Properties / Q000187:drug effects; D023001:Transplantation Tolerance / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D003432:Cross-Linking Reagents; D014227:Triazines; D011092:Polyethylene Glycols; C019309:cyanuric chloride; D013311:Streptozocin