Berman Dora M, Cabrera Over, Kenyon Norman M, Miller Joshua, Tam Susan H, Khandekar Vrinda S, Picha Kristen M, Soderman Avery R, Jordan Robert E, Bugelski Peter J, Horninger Denison, Lark Michael, Davis Janet E, Alejandro Rodolfo, Berggren Per-Olof, Zimmerman Mark, O'Neil John J, Ricordi Camillo, Kenyon Norma S
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Transplantation. 2007 Aug 15;84(3):308-15. doi: 10.1097/01.tp.0000275401.80187.1e.
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.
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.
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.
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.
胰岛上的组织因子（TF）表达可导致即刻血液介导的炎症反应（IBMIR），这会导致早期胰岛丢失。我们测试了用单克隆抗TF抗体（CNTO859）对胰岛进行移植前保护以防止IBMIR是否会增强其在我们的非人灵长类动物边缘质量模型中的植入。
六对链脲佐菌素诱导糖尿病的食蟹猴（CM），每对在代谢控制方面进行了密切匹配，并在无类固醇免疫抑制的情况下，接受了来自同一供体的5000 IEQ/kg同种异体、ABO相容的胰岛移植。对于每一对，实验动物接受用20μg/mL抗TF培养的胰岛，并在胰岛输注前10 - 25分钟静脉注射6 mg/kg抗TF；对照猴接受来自相同制剂的等量未用抗TF培养的胰岛，且未进行体内治疗。
早期空腹C肽（CP）值在配对之间（P<0.01）存在差异，但在配对内部无差异，并且与通过灌流评估的胰岛体外功能能力相关（r = 0.60；P = 0.022）。与匹配的对照相比，实验动物移植后的凝血标志物降低，空腹CP水平更高（移植后1个月和研究结束时），并且移植功能延长。
这些数据表明，用抗TF对胰岛和受体进行预处理可能会限制IBMIR的影响，从而增强胰岛植入和存活。
