Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model

Dora M. Berman, Over Cabrera, Norman M. Kenyon, Joshua Miller, Susan H. Tam, Vrinda S. Khandekar, Kristen M. Picha, Avery R. Soderman, Robert E. Jordan, Peter J. Bugelski, Denison Horninger, Michael Lark, Janet E. Davis, Rodolfo Alejandro, Per-Olof Ynge Berggren, Mark Zimmerman, John J. O'Neil, Camillo Ricordi, Norma S. Kenyon

Research output: Contribution to journalArticle

56 Scopus citations

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 μg/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.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalTransplantation
Volume84
Issue number3
DOIs
StatePublished - Aug 1 2007

Keywords

  • Coagulation
  • Graft survival
  • Islet engraftment
  • Islet transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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    Berman, D. M., Cabrera, O., Kenyon, N. M., Miller, J., Tam, S. H., Khandekar, V. S., Picha, K. M., Soderman, A. R., Jordan, R. E., Bugelski, P. J., Horninger, D., Lark, M., Davis, J. E., Alejandro, R., Berggren, P-O. Y., Zimmerman, M., O'Neil, J. J., Ricordi, C., & Kenyon, N. S. (2007). Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation, 84(3), 308-315. https://doi.org/10.1097/01.tp.0000275401.80187.1e