title: Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model.
abstract: BACKGROUND
  Tissue factor (TF) expression on islets can result in an instant blood-mediated inflammatory reaction (IBMIR) that contributes to early islet loss. We tested whether peritransplant protection of islets from IBMIR with a monoclonal anti-TF antibody (CNTO859) would enhance engraftment in our nonhuman primate marginal mass model.
  
  
  METHODS
  Each of six pairs of cynomolgus monkeys (CM) with streptozotocin-induced diabetes was closely matched for metabolic control and was transplanted with 5,000 IEQ/kg allogeneic, ABO-compatible islets from the same donor under the cover of steroid-free immunosuppression. For each pair, experimental animals received islets cultured with 20 microg/mL anti-TF and were dosed with 6 mg/kg anti-TF intravenously, 10-25 min before islet infusion; control monkeys received an equal number of islets from the same preparation cultured without anti-TF and no in vivo treatment.
  
  
  RESULTS
  Early fasting C-peptide (CP) values were different between (P<0.01), but not within, pairs and correlated with in vitro functional capacity of islets as assessed by perifusion (r=0.60; P=0.022). Compared to their matched controls, experimental animals had decreased posttransplant markers of coagulation, higher fasting CP levels (1 month posttransplant and end of study) and prolonged graft function.
  
  
  CONCLUSIONS
  These data suggest that pretreatment of islets and the recipient with anti-TF may limit the effects of IBMIR, thereby enhancing islet engraftment and survival.
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. dberman2@med.miami.edu
authors: Dora M
authors: DM
authors: Berman
authors: Over
authors: O
authors: Cabrera
authors: Norman M
authors: NM
authors: Kenyon
authors: Joshua
authors: J
authors: Miller
authors: Susan H
authors: SH
authors: Tam
authors: Vrinda S
authors: VS
authors: Khandekar
authors: Kristen M
authors: KM
authors: Picha
authors: Avery R
authors: AR
authors: Soderman
authors: Robert E
authors: RE
authors: Jordan
authors: Peter J
authors: PJ
authors: Bugelski
authors: Denison
authors: D
authors: Horninger
authors: Michael
authors: M
authors: Lark
authors: Janet E
authors: JE
authors: Davis
authors: Rodolfo
authors: R
authors: Alejandro
authors: Per-Olof
authors: PO
authors: Berggren
authors: Mark
authors: M
authors: Zimmerman
authors: John J
authors: JJ
authors: O'Neil
authors: Camillo
authors: C
authors: Ricordi
authors: Norma S
authors: NS
authors: Kenyon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008252:Macaca fascicularis; D008954:Models, Biological; D013311:Streptozocin; D013925:Thromboplastin / Q000187:drug effects / Q000502:physiology*; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D013311:Streptozocin; D013925:Thromboplastin