Diannexin Decreases Inflammatory Cell Infiltration Into the Islet Graft, Reduces β-Cell Apoptosis, and Improves Early Graft Function

• DOI: 10.1097/tp.0b013e3181ed55d8
• Publication Date: 2010-07-15T13:17:36Z
• Authors: Elaine Y. Cheng; Vijay K. Sharma; Christina Chang; Ruchuang Ding; Anthony C. Allison; David B. Leeser; Manikkam Suthanth...; Hua Yang
• Keywords: Islet cell transplantation

Background. A major unmet challenge is to reduce the islet mass needed for insulin independence in type 1 diabetic recipients after transplantation. The recombinant homodimer of human annexin V, diannexin, has completed a Phase II Clinical Trial Kidney Transplantation (NCT00615966). Methods. We developed marginal transplantation model (10–12 islets per gram recipient body weight) and investigated whether diannexin prevents β-cell apoptosis improves graft function. Diannexin was administered cell donors shortly before pancreas harvest, added isolation reagents, infused into at time repeated daily until day 4. Results. In syngeneic model, median achieve normoglycemia reduced from 17.0 days among untreated controls 3.5 diannexin-treated (P=0.004). Histologic analysis grafts harvested on 3 posttransplantation revealed decreased macrophage (44.7%±9.8% vs. 19.2%±3.2%, P=0.007) T-cell infiltration (25.9%±5.5% 9.1%±1.1%, P=0.004), lower rate (20.5%±2.8% 7.6%±2.3%, P=0.01) with treatment. Expression profiling showed significantly levels mRNA proapoptotic molecule Bid, but higher interleukin-6, interferon-γ, immunosuppressive cytokine interleukin-10. Conclusions. Our findings demonstrate that early function grafts, its effects are associated reductions inflammatory death by