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.
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: C C Lin; M Ezzelarab; R Shapiro; B Ekser; C Long; H Hara; G Echeverri; C Torres; H Watanabe; D Ayares; A Dorling; D K C Cooper Journal: Am J Transplant Date: 2010-07 Impact factor: 8.086
Authors: Zachary Fitch; Robin Schmitz; Jean Kwun; Bernhard Hering; Joren Madsen; Stuart J Knechtle Journal: Transplant Rev (Orlando) Date: 2019-04-05 Impact factor: 3.943
Authors: V L Perez; A Caicedo; D M Berman; E Arrieta; M H Abdulreda; R Rodriguez-Diaz; A Pileggi; E Hernandez; S R Dubovy; J M Parel; C Ricordi; N M Kenyon; N S Kenyon; P O Berggren Journal: Diabetologia Date: 2011-03-01 Impact factor: 10.122
Authors: Midhat H Abdulreda; Dora M Berman; Alexander Shishido; Christopher Martin; Maged Hossameldin; Ashley Tschiggfrie; Luis F Hernandez; Ana Hernandez; Camillo Ricordi; Jean-Marie Parel; Ewa Jankowska-Gan; William J Burlingham; Esdras A Arrieta-Quintero; Victor L Perez; Norma S Kenyon; Per-Olof Berggren Journal: Diabetologia Date: 2019-01-31 Impact factor: 10.122