title: Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation.
abstract: OBJECTIVE
  In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface.
  
  
  METHODS
  A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant.
  
  
  RESULTS
  Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets.
  
  
  CONCLUSIONS
  This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.
authors.affiliation: Division of Clinical Immunology, Department of Oncology, Radiology, and Clinical Immunology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Sanja
authors.initials: S
authors.lastname: Cabric
authors.forename: Javier
authors.initials: J
authors.lastname: Sanchez
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundgren
authors.forename: Aksel
authors.initials: A
authors.lastname: Foss
authors.forename: Marie
authors.initials: M
authors.lastname: Felldin
authors.forename: Ragnar
authors.initials: R
authors.lastname: Källen
authors.forename: Kaija
authors.initials: K
authors.lastname: Salmela
authors.forename: Annika
authors.initials: A
authors.lastname: Tibell
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tufveson
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects; D006085:Graft Survival; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D010477:Perfusion; D013552:Swine; D046509:Tissue Culture Techniques; D014182:Transplantation, Autologous / Q000276:immunology / Q000379:methods / Q000473:pathology; D014183:Transplantation, Heterologous / Q000276:immunology / Q000379:methods / Q000473:pathology
chemical_list: D000017:ABO Blood-Group System; D006493:Heparin